Gastric cancer (GC) is an aggressive malignancy with poor clinical outcome. F-box and WD repeat domain-containing protein 2 (FBXW2), a substrate receptor of the SKP1-Cullin 1-F-box (SCF) E3 ubiquitin ligase complex, has been implicated in tumor suppression across multiple malignancies; however, its role in GC progression remains undefined. Here, we integrated transcriptomic analyses using the TNMplot database and clinical specimens to demonstrate that FBXW2 expression was significantly downregulated in GC tissues, with low FBXW2 levels correlating closely with poor survival in GC patients. Functional characterization via gain- and loss-of-function strategies revealed that FBXW2 overexpression potently inhibited proliferation, cancer stem cell phenotype, migratory capacity, and invasive potential in human GC cell lines. Consistently, xenograft tumor models showed that FBXW2 overexpression delayed tumor growth and suppresses pulmonary metastasis. FBXW2 silencing promoted malignant progression both in vitro and in vivo. Label-free quantitative proteomics combined with mechanistic investigations identified WASP-like actin nucleation-promoting factor (WASL), a key regulator of cytoskeletal dynamics, as a direct downstream target of FBXW2. FBXW2 physically interacted with WASL and facilitated its ubiquitination-dependent proteasomal degradation. Ectopic WASL expression abrogated FBXW2-mediated suppression of GC cell viability and metastatic potential. Chromatin immunoprecipitation-PCR and DNA Pull Down analyses further revealed that Forkhead box P2 (FOXP2), a transcription factor frequently upregulated in GC, directly bound the FBXW2 promoter to repress its transcription, linking epigenetic dysregulation to FBXW2 downregulation in malignant tissues. Collectively, this study establishes FBXW2 as a critical tumor suppressor in GC, operating through ubiquitin-mediated degradation of WASL to inhibit cancer progression. Targeting the FOXP2-FBXW2-WASL axis may represent a promising therapeutic strategy for combating GC malignancy.

BackgroundHepatic portal venous gas (HPVG) is often regarded as a critical warning sign and has poor patient prognosis if appropriate treatment measures are not promptly administered. There is significant heterogeneity in clinical manifestations, diagnostic approaches, and outcomes among patients with HPVG; hence, this study aimed to analyze the clinical characteristics of patients with HPVG and explore more effective treatment methods to provide valuable references for future clinical treatment strategies.MethodsA total of 21 patients diagnosed with HPVG using computed tomography at the First People’s Hospital of Hangzhou between January 2014 and October 2024 were retrospectively analyzed. A comprehensive analyses of the sex, age, laboratory test results, reasons for admission, comorbidities, treatment methods, and outcomes of patients were done.ResultsThe mean age of the 21 patients (13 men and 8 women) was 61.7 years. Patients presented with decreased red blood cell and hemoglobin counts, and increased white blood cell, neutrophil, C-reactive protein, and D-dimer levels. The main etiologies of HPVG were peritonitis (52.4%), post-abdominal surgery (47.6%), intestinal necrosis (33.3%), and gastrointestinal bleeding (28.6%), while the common comorbidities were peritonitis (52.4%), hypertension (52.4%), and coronary heart disease (23.8%). The overall mortality rate of patients with HPVG was 28.6%, and most of the deceased patients had bowel necrosis. Platelet count [odds ratio (OR): 0.979; 95% confidence interval (CI): 0.962–0.997; p = 0.024] and neutrophil levels, (OR: 1.161; 95% CI: 1.019–1.323; p = 0.025), and the presence of hypertension (OR: 15.750; 95% CI: 1.424–174.246; p = 0.025) and peritonitis (OR: 15.750; 95% CI: 1.424–174.246; p = 0.025) were significantly associated with the likelihood of requiring surgical intervention. Most patients had a good prognosis after surgical treatment.ConclusionThis study systematically described the clinical characteristics, etiologies, comorbidities, and prognosis of patients with HPVG and identified predictors indicating the need for surgical intervention.

Emerging evidence has suggested a potential pathological association between early-onset left-sided colorectal cancer (EOLCC) and metabolic syndrome (MetS). However, the underlying genetic and molecular mechanisms remain insufficiently elucidated. This study aimed to identify and characterize key biomarkers associated with the progression and treatment response of MetS-related EOLCC. An in-hospital cohort was utilized to assess the clinical implications of primary tumor location in early-onset colorectal cancer (EOCRC). Differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) were employed to identify genes potentially associated with MetS-related EOLCC. Functional enrichment analyses were conducted to explore the underlying mechanisms. Candidate biomarkers were screened using random forest (RF) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Survival relevance, expression profiles, and diagnostic performance were analyzed to identify key biomarkers. Treatment responses were evaluated, and potential therapeutic compounds were identified through molecular docking. Single-cell RNA sequencing (scRNA-seq) data and in vitro experiments were used to validate gene expression and functional characteristics. The in-hospital cohort revealed a higher proportion of EOLCC among EOCRC patients. Using the edgeR package and WGCNA, we identified coexpressed genes common to both EOLCC and MetS, significantly enriched in pathways associated with stromal remodeling and metabolic regulation. Machine learning algorithms highlighted three candidate biomarkers. Among them, only CD151 was associated with prognosis and advanced disease stage. CD151 was strongly correlated with stromal remodeling and chemoresistance. Additionally, potential therapeutic compounds targeting MetS-related EOLCC were identified via molecular docking. scRNA-seq analysis confirmed the expression and functional patterns of CD151, particularly in tumor cells. The bioinformatics results were further validated through quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemical (IHC) staining. This study identified CD151 as a key biomarker in MetS-related EOLCC, offering valuable insights into prognosis, tumor biology, and personalized treatment strategies. CD151 may serve as a reference for future research and clinical applications targeting this disease subtype.

Background:Idiopathic hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent eosinophilia, which can lead to multi-organ dysfunction. Despite its highly heterogeneous clinical manifestations, cardiac and neurological complications are the most significant contributors to patient disability and mortality. Case Description:We report the case of a 66-year-old man who was emergently admitted to the hospital with the chief complaint of "sudden unsteady walking accompanied by deviation of the corner of the mouth for 15 hours". Laboratory tests revealed a significantly elevated eosinophil percentage (47.4%, count: 6.76×109/L). Initial diagnostic evaluation, including head computed tomography (CT) combined with CT angiography and CT perfusion, showed no significant abnormalities. However, magnetic resonance imaging confirmed an acute infarct in the left basal ganglia-paraventricular area. To control hypereosinophilia, dexamethasone (10 mg/day) was initiated. Due to the patient's suboptimal therapeutic response, treatment was escalated to prednisolone (15 mg three times a day) for intensive management 2 days later. Following clinical stabilization, the regimen was transitioned back to dexamethasone for maintenance therapy (2.25 mg once daily at discharge), in accordance with standard steroid tapering protocols in HES. On the seventh day, the patient developed sudden signs of generalized peritonitis, and imaging revealed intestinal ischemia. By the tenth day, the classic triad of strangulated intestinal obstruction had emerged; that is, progressive abdominal pain, positive fecal occult blood (+++), and CT findings of a pneumoportogram with terminal ileal wall edema. Emergency exploratory laparotomy confirmed extensive intestinal necrosis, necessitating radical intestinal resection and jejunostomy. Following stepwise management, digestive tract reconstruction (jejunostomy reduction and end-to-side anastomosis of the small intestine and colon) was successfully performed. Current follow-up indicates a good prognosis. Conclusions:This case provides valuable clinical insights into the early identification and management of thrombotic critical conditions secondary to idiopathic HES. It also highlights multi-dimensional intervention strategies for short bowel syndrome, expanding post-intestinal resection management pathways.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is associated with the poor prognosis of colorectal cancer (CRC) patients, but the therapeutic strategies targeting KRAS are limited, and novel intervention strategies are urgently needed. The dysfunction of deubiquitinases (DUBs) is widely involved in the progression of malignancy, and DUBs are considered ideal anti-tumor targets due to their well-defined structures and catalytic sites. In our study, through DUB inhibitors screening and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis, we identified that ubiquitin-specific protease 10 (USP10) functions as a potent DUB regulating KRAS mutants' activity. Mechanistically, USP10 directly binds to and promotes KRAS variants' activity across different mutants by removing the latter’s non-proteolytic ubiquitination chains mainly containing K6, K11, K27 and K29-linkage; while the activated KRAS mutants reciprocally upregulate USP10 levels by phosphorylating the latter at Thr42/Ser337, therefore forming a positive feedback circuit and synergistically promoting KRAS-mutant CRC growth. Moreover, we found that USP10 is elevated in KRAS-mutant CRC tissues and depletion of USP10 preferentially impeded KRAS-mutant CRC growth in vitro/in vivo. Our findings not only uncover the critical roles of the USP10/KRAS positive feedback circuit in promoting KRAS-mutant CRC growth, but also offer novel therapeutic strategies for CRC patients harboring KRAS variants across different mutants by targeting USP10.

Antibody-mediated cis-delivery and trans-delivery both direct cytokines to tumors and have been extensively investigated in clinical trials. However, a comparative analysis of their differential effects on cytokine activity is still lacking. In this study, we initially verify that cis-delivery of cytokine demonstrates a markedly stronger antitumor effect than trans-delivery, but it also exhibits certain drawbacks, including severe toxicity, insufficient activation of CD25+CD8+ T cells, and enhanced stimulation of intratumoral regulatory T cells (Tregs). To further address these issues, we developed a conditionally releasable and cis-delivering IL-15 immunocytokine (termed PMIS), which can selectively release a free IL-15 superagonist within tumors rather than immobilizing IL-15 to PD-1+ Tregs, thereby potently stimulating CD25+CD8+ T cells. Mice treated with PMIS showed significantly reduced systemic toxicities while achieving notably stronger antitumor effects. Administered either alone or in combination with other therapies, PMIS exhibits great potential for inhibiting orthotopic cold tumor and its metastases. Mechanistically, the significant activation of the pre-existing intratumoral CD25+CD8+ T cells and the improved CD25+CD8/Treg ratio contribute to the enhanced antitumor response of PMIS. These findings underscore the indispensable role of CD25+CD8+ T cells in cis-delivering IL-15 and provide a promising strategy for overcoming resistance to therapies and effectively controlling advanced cold tumors. ### Competing Interest Statement The authors have declared no competing interest. The datasets used or analyzed in this study are available from the corresponding author upon request. National Natural Science Foundation of China, 3, 82404500; W2412118; 82203708 Natural Science Foundation of Chongqing, 2022NSCQ-MSX2319 Science & Technology Commission of Shanghai Municipality, No. 23ZR1431800 Zhejiang Medical and Health Technology Project, 2023RC058; 2024KY175

Previous studies have suggested that AQP5 expression is increased in colorectal cancer tissues and is associated with the progression and prognosis of colorectal cancer. However, there are few studies on the relationship between AQP5 and chemotherapy resistance in colorectal cancer cells and the related mechanisms. In this study, AQP5 overexpression plasmid was transfected into human colorectal cancer cell lines RKO and HCT116, and the effects of AQP5 combined with 5-FU on the proliferation and apoptosis of colorectal cancer cells and the underlying mechanism were investigated by western blotting, MTT assay and flow cytometry. Then, the results of in vitro experiments were verified in vivo using SPF nude mice. AQP5 overexpression plasmid transfected significantly increased AQP5 expression in colorectal cancer cell lines, MTT assay showed that AQP5 overexpression promoted the proliferation of colorectal cancer cells. 5-FU inhibited the proliferation of colorectal cancer cells. Overexpression of AQP5 can restore the inhibition of 5-FU to some extent. Flow cytometry showed that AQP5 had no significant effect on apoptosis of colorectal cancer cells. Western blotting experiments showed that the expression level of p-NF-κB protein in AQP5 overexpression group was significantly up-regulated. The results of tumor bearing experiment in nude mice (in vivo) showed that the tumor growth rate of AQP5 overexpression group was faster, and the tumor diameter and body weight of nude mice were significantly increased. After 5-FU treatment, the tumor volume became smaller, and the tumor volume in AQP5 overexpression group was significantly larger than that in control group. Immunohistochemical results showed that the expression level of p-NF-κB was up-regulated and the number of apoptosis was decreased in the 5-FU treatment group with AQP5 overexpression. Overexpression of AQP5 can promote the growth of colorectal cancer cells and promote the occurrence of drug resistance, which may be related to NF-κB signaling pathway. AQP5-mediated chemoresistance suggests its potential as a target for RNA-based gene silencing therapies.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 1D, DCFH‑DA‑stained cellular data in Fig. 2A, and western blotting data in Figs. 2G and 5B were strikingly similar to data that had either already appeared in previously published articles written by different authors at different research institutes (one of which has since been retracted), or were featured in an article that was submitted for publication to a different journal at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 50: 89, 2022; DOI: 10.3892/ijmm.2022.5144].

Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). Tremella fuciformis polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT-qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.

Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is a new adjuvant therapy for the treatment of abdominal malignant tumors and metastases, which has shown great potential. The HIPEC technique can effectively kill residual lesions in the abdominal cavity through the synergistic sensitization effect of thermal chemotherapy and the circulating perfusion and washing effect of large volume perfusion fluid, thereby reducing the occurrence of malignant ascites and reducing the risk of postoperative recurrence and metastasis. However, there are still many problems in the practical operation of HIPEC, such as non-uniform distribution of perfusate temperature, inadequate perfusion due to the presence of ‘dead space’, incomplete cytoreductive surgery (CRS), instances of catheter obstruction during perfusate circulation, the lack of a uniform standard for selecting appropriate HIPEC techniques, occupational exposure of medical personnel during the HIPEC procedure, and the selection of HIPEC chemotherapy regimens for patients with various types of tumors. This article aims to summarize the problems encountered in the clinical practice of HIPEC, explore the problems that can be improved, and put forward some suggestions, so as to promote the further standardization and normalization of HIPEC technology.

Duodenal stump fistula is a rare but dangerous complication of gastric cancer surgery. Reinforcement of the duodenal stump was suggested as a useful method to prevent the occurrence of duodenal stump fistula. Although laparoscopic surgery has been established as a safe procedure for gastric cancer, it is acknowledged that the application of duodenal stump reinforcement is a demanding process in laparoscopic radical gastrectomy. This review aims to provide a concise description of the proposed reinforcement methods of duodenal stump after laparoscopic radical gastrectomy for gastric cancer by summarizing the relevant literature written in English. The thorough knowledge of these reinforcement techniques may help surgeons to find the most suitable reinforcement method of duodenal stump for patients.

肠道菌群与结直肠癌的发生、发展关系密切,是结直肠癌的潜在治疗靶点,以肠道微生物为主要靶点的治疗策略被越来越多的学者所关注.本文对肠道菌群在结直肠癌中的作用机制、临床应用及安全性进行综述,旨在为结直肠癌的临床治疗提供理论依据.

Introduction: Colorectal cancer is one of the most prevalent life-threatening malignant tumors with high incidence and mortality. However, the efficacy of current therapeutic regimens is very limited. Regorafenib has been approved for second- or third-line treatment of patients who are refractory to standard chemotherapy diagnosed with metastatic colorectal cancer, but its clinical efficacy needs to be further improved. Accumulating evidence demonstrates that statins also possess potent anticancer activities. However, whether regorafenib and statins pose synergistic anticancer effects in colorectal cancer is still unclear.Methods: Sulforhodamine B (SRB) assays were applied to evaluate the anti-proliferative activity of regorafenib or/and rosuvastatin in vitro, and immunoblotting analysis were applied to detect the effects of regorafenib/rosuvastatin combined treatment on mitogen-activated protein kinase (MAPK) signaling and apoptosis-related proteins. MC38 tumors were applied to investigate the synergistic anticancer effects of regorafenib in combination with rosuvastatin in vivo.Results: We found that regorafenib in combination with rosuvastatin exerted significant synergistic inhibition against colorectal cancer growth in vitro and in vivo. Mechanistically, regorafenib and rosuvastatin combination synergistically suppressed MAPK signaling, a crucial signaling pathway promoting cell survival, as indicated by the reduction of phosphorylated MEK/ERK. In addition, regorafenib in combination with rosuvastatin synergistically induced the apoptosis of colorectal cancer in vitro and in vivo.Discussion: Our study demonstrated the synergistic anti-proliferative and pro-apoptotic effects of regorafenib/rosuvastatin combined treatment in colorectal cancer in vitro/vivo and might potentially be evaluated as a novel combination regimen for clinical treatment of colorectal cancer.

Larotrectinib (Lar) is a highly selective and potent small-molecule inhibitor used in patients with tropomyosin receptor kinase (TRK) fusion-positive cancers, including colon cancer. However, the underlying molecular mechanisms specifically in patients with colon cancer have not yet been explored. Our data showed that Lar significantly suppressed proliferation and migration of colon cancer cells. In addition, Lar suppressed the epithelial-mesenchymal transition (EMT) process, as evidenced by elevation in E-cadherin (E-cad), and downregulation of vimentin and matrix metalloproteinase (MMP) 2/9 expression. Furthermore, Lar was found to activate autophagic flux, in which Lar increased the ratio between LC3II/LC3I and decreased the expression of p62 in colon cancer cells. More importantly, Lar also increased AMPK phosphorylation and suppressed mTOR phosphorylation in colon cancer cells. However, when we silenced AMPK in colon cancer cells, Lar-induced accumulation of autolysomes as well as Lar-induced suppression of the EMT process were significantly diminished. An in vivo assay also confirmed that tumour volume and weight decreased in Lar-treated mice than in control mice. Taken together, this study suggests that Lar significantly suppresses colon cancer proliferation and migration by activating AMPK/mTOR-mediated autophagic cell death.

Gastric cancer is one of the first malignant cancers in the world and a large number of people die every year due to this disease. Many genetic and epigenetic risk factors have been identified that play a major role in gastric cancer. HOTAIR is an effective epigenetic agent known as long noncoding RNA (lncRNA). HOTAIR has been described to have biological functions in biochemical and cellular processes through interactions with many factors, leading to genomic stability, proliferation, survival, invasion, migration, metastasis, and drug resistance. In the present article, we reviewed the prognostic value of the molecular mechanisms underlying the HOTAIR regulation and its function in the development of Gastric Cancer, whereas elucidation of HOTAIR–protein and HOTAIR–DNA interactions can be helpful in the identification of cancer processes, leading to the development of potential therapeutic strategies.

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide ([Formula: see text]-dependent deacetylase involved in multiple glucose metabolism pathways and plays an important role in the pathogenesis of diabetes mellitus (DM). The enzyme specifically recognizes its deacetylation substrates' peptide segments containing a central acetyl-lysine residue as well as a number of amino acids flanking the central residue. In this study, we attempted to ascertain the minimal sequence requirement (MSR) around the central acetyl-lysine residue of SIRT1 substrate-recognition sites as well as the amino acid preference (AAP) at different residues of the MSR window through quantitative structure-activity relationship (QSAR) strategy, which would benefit our understanding of SIRT1 substrate specificity at the molecular level and is also helpful to rationally design substrate-mimicking peptidic agents against DM by competitively targeting SIRT1 active site. In this procedure, a large-scale dataset containing 6801 13-mer acetyl-lysine peptides (and their SIRT1-catalyized deacetylation activities) were compiled to train 10 QSAR regression models developed by systematic combination of machine learning methods (PLS and SVM) and five amino acids descriptors (DPPS, T-scale, MolSurf, [Formula: see text]-score, and FASGAI). The two best QSAR models (PLS+FASGAI and SVM+DPPS) were then employed to statistically examine the contribution of residue positions to the deacetylation activity of acetyl-lysine peptide substrates, revealing that the MSR can be represented by 5-mer acetyl-lysine peptides that meet a consensus motif [Formula: see text][Formula: see text][Formula: see text](AcK)0[Formula: see text]. Structural analysis found that the [Formula: see text] and (AcK)0 residues are tightly packed against the enzyme active site and confer both stability and specificity for the enzyme-substrate complex, whereas the [Formula: see text], [Formula: see text] and [Formula: see text] residues are partially exposed to solvent but can also effectively stabilize the complex system. Subsequently, a systematic deacetylation activity change profile (SDACP) was created based on QSAR modeling, from which the AAP for each residue position of MSR was depicted. With the profile, we were able to rationally design an SDACP combinatorial library with promising deacetylation activity, from which nine MSR acetyl-lysine peptides as well as two known SIRT1 acetyl-lysine peptide substrates were tested by using SIRT1 deacetylation assay. It is revealed that the designed peptides exhibit a comparable or even higher activity than the controls, although the former is considerably shorter than the latter.

Interleukin-15 (IL-15) is a promising candidate for cancer immunotherapy due to its potent immune-activating effects. There are several IL-15 molecules currently in clinical trials but facing shortages of poor half-life, circulation instability, or complicated production and quality control processes. The aim of this study is to design a novel IL-15 superagonist to set out the above difficulties, and we constructed F4RLI consisting of the GS-linker spaced IgG4 Fc fragment, soluble IL-15 Rα (sIL-15Rα), and IL-15(N72D). Using a single plasmid transient transfection in HEK293E cells, the matured F4RLI was secreted in the form of homodimer and got purified by an easy step of protein A affinity chromatography. The F4RLI product can significantly stimulate the proliferation of human CD3+CD8+ T cells and NK cells in vitro. Meanwhile, F4RLI greatly extended the half-life and prolonged the exposure of IL-15 in mice nearly by 28- and 200-fold, respectively, in comparison with that of the IL-15 monomer. In vivo, F4RLI vastly expanded mouse splenic CD8+ T lymphocytes, illustrating its potential in tumor immunotherapy. Further studies showed that the combination of F4RLI with the immune checkpoint blocker atezolizumab played a synergistic effect in treating MC38 mouse tumor by increasing the percentage of CD8+ T cells in tumor tissue. Moreover, the combination therapy of F4RLI with the angiogenesis inhibitor bevacizumab resulted in significant tumor growth suppression in a xenograft human HT-29 mouse model. Overall, our results demonstrate a homodimeric IL-15 superagonist F4RLI with advances in manufacturing processes and biopharmaceutical applications for cancer immunotherapy. KEY POINTS: • The homodimeric structure of F4RLI facilitates its easy production processes and quality control. • The fusion with Fc and sIL-15Rα extends the plasma half-life of IL-15 by about 28-fold. • F4RLI can play synergistic antitumor activity with the PD-1/PD-L1 checkpoint inhibitor or angiogenesis inhibitor.

migration and chemotherapy sensitivity of hepatocellular carcinoma Hep-3B cells and its mechanism. In present study Hep-3B cells cultured in vitro were divided into control group (normal culture), NC-siRNA group (transfected with NC-siRNA), and TINCR-siRNA group (transfected with TINCR-siRNA), In addition, cells treated with cisplatin after transfection of TINCR-siRNA were designated as the TINCR-siRNA + cisplatin group, and only cells treated with cisplatin were designated as cisplatin group. The expression levels of TINCR and miR-646 in the cells of the control group, NC-siRNA group and TINCR-siRNA group were tested by RT-PCR, and the cell proliferation, invasion and migration ability of the three groups were detected by the CCK-8 method and Transwell chamber experiment. Cell proliferation and apoptosis of NC-siRNA group, TINCR-siRNA group, cisplatin group and TINCR-siRNA+cisplatin group were checked by CCK-8 method and flow cytometry; and targeted binding relationship between TINCR and miR-646 was measured by dual luciferase reporter gene experiment. According to results of our study, compared with the control group there was no significant difference in the parameters of Hep-3B cells after transfection of NC-siRNA (P> 0.05), but the expression level of TINCR and cell proliferation, invasion and migration ability were significantly reduced, and the expression level of miR-646 in the cells was significantly increased, which were statistically significant compared with the control group or the NC-siRNA group (P<0.05). In addition, transfection of TINCR-siRNA can also enhance the antiproliferative and pro-apoptotic effect of cisplatin on Hep-3B cells. Double luciferase reporter gene experiments confirmed that TINCR can target miR-646. We concluded Down-regulating the expression of TINCR can inhibit the proliferation, invasion and migration of hepatocellular carcinoma Hep-3B cells and enhance its sensitivity to chemotherapy with cisplatin, and the mechanism may be related to the targeted regulation of miR-646 expression.

Background: We aimed to evaluate the effects of lncRNA PTV1 on colon cancer proliferation and migration via the Wnt6/β-catenin2 pathway. Materials and Methods: A total of 117 colon cancer and normal adjacent tissue samples were collected. LncRNA PVT1 and miR-1207-5p expressions in these samples and colon cancer cell lines were detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). LncRNA PVT1-silencing cells and miR-1207-5p-overexpressing Caco-2-siPVT1 cells were constructed, respectively. The effects of lncRNA PVT1 silencing on cell proliferation were assessed by MTT and colony formation assays. The effects on invasion and migration were tested by Transwell and scratch assays respectively. The targeting regulatory relationship between miR-1207-5p and Wnt6 was analyzed by a dual-luciferase reporter assay. The relationship between lncRNA PVT1 and miR-1207-5p was studied by RNA-binding protein immunoprecipitation and RNA pull-down assays. The expressions of proteins in the Wnt6/β-catenin2 pathway were detected by Western blotting. Results: The lncRNA PVT1 mRNA expression in colon cancer tissue was significantly higher than that in normal adjacent tissue (p < 0.05). The expression in lncRNA PVT1-silencing cells was significantly down-regulated (p < 0.05). The colonies of Caco-2-siPVT1 cells decreased, accompanied by a reduced number of cells penetrating Matrigel and migration (p < 0.05). Compared with siPVT1 + NC group, the number of colonies and migration of siPVT1 + miR-1207-5p-overexpressing group increased significantly (p < 0.05). There was a targeting relationship between miR-1207-5p and PVT1. MiR-1207-5p had a targeted binding site with Wnt6. The protein expressions of Wnt6/β-catenin2 in Caco-2-siPVT1 group were significantly lower than those of control and Caco-2-siNC groups (p < 0.05). Conclusion: LncRNA PVT1 was highly expressed in colon cancer. It may enhance the proliferation and migration of colon cancer cells by up-regulating miR-1207-5p level and enhancing the Wnt6/β-catenin2 pathway.