Objective:This study investigates the role of circCDK6 in maintaining cancer stem cell (CSC) properties and mediating cisplatin resistance in lung adenocarcinoma (LUAD), with a focus on the involvement of the Wnt/β-catenin signaling pathway. Methods:The expression levels of circCDK6 in various LUAD cell lines were measured using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted by plasmid-mediated overexpression and siRNA-mediated knockdown of circCDK6. Cisplatin sensitivity was assessed using the Cell Counting Kit-8 assay and colony formation assay. The involvement of the Wnt/β-catenin pathway was examined by inhibiting the pathway with IWR-1. A subcutaneous xenograft model in BALB/c nude mice was used to evaluate the in vivo effects of circCDK6 knockdown on cisplatin responsiveness, and tumor tissues were analyzed through hematoxylin and eosin staining and immunohistochemistry for Ki-67 expression. Results:CircCDK6 expression was significantly elevated in H1299 and H1975 cells compared to A549 and PC-9 cells. Overexpression of circCDK6 increased stemness markers, such as CD133, Oct4, and Sox2, and enhanced cisplatin resistance, as demonstrated by higher IC50 values and increased colony formation. In contrast, circCDK6 silencing significantly reduced cisplatin resistance. Western blot analysis revealed that circCDK6 activated the Wnt/β-catenin pathway by upregulating Axin2, β-catenin, and c-Myc. In vivo, circCDK6 knockdown reduced tumor volume, improved the anti-tumor effect of cisplatin, and decreased Ki-67 expression. Conclusion:CircCDK6 may promote CSC properties and contribute to cisplatin resistance in LUAD, potentially through activation of the Wnt/β-catenin pathway. These findings suggest that circCDK6 may represent a potential therapeutic target for overcoming chemoresistance in LUAD, although further studies are needed to validate its role and clinical relevance.

Histones are the fundamental building blocks of chromatin and serve as pivotal regulators of gene expression. Differential expression and mutations of H3.1 and H3.3 genes have been implicated in the pathogenesis of various cancer types. Mutations in H3.3, especially lysine to methionine substitutions (K27M/K36M), are particularly prevalent. Moreover, genetic alterations such as G34R/W/V/L, as well as variations in H3F3A and H3F3B genes, have also been identified. Despite high similarity in amino acid sequences, H3.1 and H3.3 have discrete functions in cancer. In this review, we delve into the recent advances in elucidating the implications of canonical histone H3.1 and its variant H3.3 on chromatin structure and function. Additionally, we explore how potential enhancing factors such as PTEN, MLL5, GPR87 and histone chaperones influence H3.1/H3.3 function.

Tongue squamous cell carcinoma (TSCC) is characterized by early lymph node metastasis (LNM), which significantly impacts prognosis. Traditional diagnostic methods rely on invasive biopsies or postoperative histopathology, highlighting the need for non-invasive preoperative prediction tools. This study aimed to develop an interpretable radiomics model using tumor shape features from magnetic resonance imaging (MRI) to predict cervical LNM in TSCC. We retrospectively analyzed data from 293 TSCC patients across two hospitals. Shape-related radiomic features were extracted from preoperative contrast-enhanced T1-weighted imaging (CET1WI) and T2-weighted imaging (T2WI). A radiomics model was developed using logistic regression (LR) and validated internally and externally. Clinical variables were integrated into a combined model. The SHapley Additive exPlanations (SHAP) framework was employed to interpret feature contributions. The radiomics model achieved AUCs of 0.818 (training cohort), 0.739 (validation cohort), and 0.755 (test cohort). Incorporating clinical variables did not significantly improve performance. SHAP analysis identified T2WI_SurfaceVolumeRatio as the most influential feature. Individualized force plots and a web-based nomogram provided intuitive visualizations of model predictions. Tumor shape features derived from MRI, particularly SurfaceVolumeRatio, independently predict cervical LNM in TSCC. The SHAP-interpretable radiomics model offers a clinically transparent, non-invasive tool for preoperative risk stratification, aiding personalized treatment decisions.

Background: Ovarian cancer (OC) ranks among the most lethal gynecological malignancies. Research has highlighted long noncoding RNAs (lncRNAs) as promising novel molecular targets for cancer therapy. This study endeavors to identify novel lncRNAs, elucidate their specific roles, and unravel their regulatory mechanism in OC development. Methods: Utilizing LncRNA Microarray technology, we screened for differentially expressed RNAs, ultimately selecting THAP7-AS1 for in-depth investigation. RNA pull-down, luciferase assays and FISH were performed to validate the interaction among THAP7-AS1, miR-92b-5p and FA2H. qRT-PCR was conducted to assess the expression of THAP7-AS1, miR-92b-5p and FA2H in OC tissues and cell lines. Cellular biological effects were examined using proliferation CCK-8 and EdU assays, chamber Transwell migration assays, and flow cytometer for apoptosis analysis. Additionally, nude mice xenograft models were established to evaluate the in vivo effect of THAP7-AS1 on tumor growth. Results: Our findings revealed a downregulation of THAP7-AS1 in OC tissues and cells. Overexpression of THAP7-AS1 inhibited cell proliferation, migration, and induced apoptosis. miR-92b-5p was identified as a sponge target of THAP7-AS1, with its expression upregulated in OC tissues and cells. Forced expression of miR-92b-5p exhibited cellular effects opposite to those of THAP7-AS1 overexpression. Additionally, FA2H was confirmed as a direct target of miR-92b-5p Silencing FA2H suppressed apoptosis, promoted proliferation and migration. In vivo experiments showed overexpression of THAP7-AS1 significantly reduced tumor volume and weight. Conclusion: THAP7-AS1 is firstly reported as a tumor suppressor in OC by targeting the miR-92b-5p/FA2H axis. Our findings suggest that THAP7-AS1 holds potential as therapeutic target in OC treatment.

Distinguishing benign and malignant endometrial lesions on the basis of endometrial thickness (ET) may lead to a missed diagnosis of endometrial carcinoma (EC) in women with postmenopausal bleeding (PMB) or increased invasive examination and pain in women with benign endometrial lesions. Our research aims to establish an ultrasonic prediction model for differentiating between benign endometrial lesions and EC in women with PMB. PMB women with ET ≥ 5 mm (n = 412) or ET < 5 mm who presented with recurrent vaginal bleeding (n = 57) were enrolled in this prospective observational study. According to the pathological examination results of the endometrium, women with PMB were divided into endometrial atrophy (EA) (n = 231), endometrial polyp (EP) (n = 98), endometrial hyperplasia (EH) (n = 58) and EC (n = 82) groups. Ultrasonic parameters were compared among the four groups. The predictive value of different parameters for differentiation between benign endometrial lesions and EC in women with PMB was determined via receiver operating characteristic (ROC) curves. The best cut-off of ultrasonic parameters analyzed by ROC curves was used to establish prediction model. Women with EC had significantly thicker endometrium and higher endometrial volume (EV), vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) than women with other pathological types of endometrium (P < 0.05). The endometrial VI, FI and VFI of women with EH were significantly higher compared with those in women with EA and EP (P < 0.05). For patients with ET ≥ 5 mm, the best parameter for distinguishing between benign lesions and EC was the FI, with an area under the curve (AUC) of 0.86, a sensitivity of 86.7% and a specificity of 81.4%. In addition, for patients with ET < 5 mm, the best parameter for distinguishing between benign lesions and EC was the VI, with an AUC of 0.92, a sensitivity of 92.1% and a specificity of 72.9%. The ultrasonic prediction model based on the FI and VI had better predictive value for EC in both patients with ET ≥ 5 mm and patients with ET < 5 mm. The ultrasonic parameters differed among the different pathological types of the endometrium in women with PMB. The ultrasonic prediction model based on the endometrial FI and VI was clinically useful for differentiating between benign endometrial lesions and EC, especially in postmenopausal patients with recurrent vaginal bleeding presenting with ET of less than 5 mm.

Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. Proliferation, migration and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. A xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis in nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and western blot assays were conducted. FAM64A was upregulated in ovarian cancer tissues and cells and was demonstrated to promote the proliferation, migration and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assays indicated that FAM64A could regulate the EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the knockdown of FAM64A inhibited tumor growth in xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogenic function by regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.

Background: Platelet-rich plasma (PRP) helps promote wound healing, but it is unclear whether it stimulates breast cancer cell proliferation, which restricts its application in breast cancer patients. This article explored the effect of PRP on breast cancer cell proliferation through preclinical experiments. Method: We cultivated MDA-MB-231 breast cancer cells with PRP in vitro. Subsequently, we employed Cell Counting Kit-8 (CCK-8) assays to assess their proliferation ability, wound healing assays to evaluate their migration ability, and Transwell assays to detect their invasion ability. Mouse breast cancer 4T1 cells were subcutaneously inoculated into nude mice. After tumor formation, PRP was injected around each tumor. Tumor size was measured. After 15 days, the tumors were surgically removed. Immunohistochemistry was used to detect key proteins involved in proliferation and apoptosis. Results: PRP inhibited the proliferation, migration, and invasion of MDA-MB-231 in vitro. After PRP was injected around tumors in nude mice, tumor growth slowed, Ki67 and phospho-histone H3 (pHH3) expression decreased, and Caspase 3 and Poly (adenosine diphosphate-ribose) polymerase 1 (PARP1) expression increased. Conclusion: The PRP inhibits the proliferation of breast cancer MDA-MB-231 and 4T1 cells.

Objective To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC). Methods 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up. Results No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups ( P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group ( P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group ( P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group ( P < 0.05). Conclusion Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.

The morbidity and mortality of NSCLC remains high worldwide. However, the molecular mechanisms of NSCLC still largely unclear. Ets variant 5 (ETV5) is a transcription factor that found to be overexpressed in multiple cancers. However, the role of ETV5 in NSCLC remains unknown. We aim to explore the role and mechanisms of ETV5 in NSCLC development. The expression of ETV5 was evaluated in NSCLC tissues and cell lines. ETV5 overexpressing and downregulation cell lines were established according to the endogenous expression of ETV5. Functional studies were performed by transwell assay. The downstream targets of ETV5 were screened by PCR array and were confirmed by luciferase reporter assay. We found that overexpression of ETV5 indicates worse prognosis of NSCLC patients. Elevated ETV5 expression promotes NSCLC cell invasion and migration via transcriptional activates of TGFβ1. Therefore, ETV5/TGFβ signaling may serve as a therapeutic target for NSCLS patients.

Circular RNAs (circRNAs) are novel noncoding RNAs with covalently closed-loop structures that can regulate eukaryotic gene expression. Due to their stable structure, circRNAs are widely distributed in the cytoplasm and have important biological functions, including as microRNA sponges, RNA-binding protein conjugates, transcription regulators, and translation templates. Breast cancer is among the most common malignant cancers diagnosed in women worldwide. Despite the development of comprehensive treatments, breast cancer still has high mortality rates. Recent studies have unmasked critical roles for circRNAs in breast cancer as regulators of tumour initiation, progression, and metastasis. Further, research has revealed that some circRNAs have the potential for use as diagnostic and prognostic biomarkers in clinical practice. Herein, we review the biogenesis and biological functions of circRNAs, as well as their roles in different breast cancer subtypes. Moreover, we provide a comprehensive summary of the clinical significance of circRNAs in breast cancer. CircRNAs are believed to be a hot focus in basic and clinical research of breast cancer, and innovative future research directions of circRNAs could be used as biomarkers, therapeutic targets, or novel drugs.Abbreviations: CeRNA: Competitive endogenous RNA; ciRNA: Circular intronic RNA; circRNA: Circular RNA; EIciRNA: Exon-intron circRNA; EMT: Epithelial-mesenchymal transition; IRES: Internal ribosome entry site; lncRNA: Long non-coding RNA; miRNA: MicroRNA; MRE: MiRNA response element; ncRNA: Non-coding RNA; RBP: RNA-binding protein; RNA-seq: RNA sequencing; RT-PCR: Reverse transcription-polymerase chain reaction.

The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases. GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway, and inhibited the proliferation and migration of GC cells. Conversely, GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway, and promoted GC cell proliferation and migration. Furthermore, platelet-derived growth factor subunit BB (PDGF-BB) cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression. Moreover, GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice, while GIPC1 overexpression had contrasting effects. Taken together, our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.

The purpose of this study was to investigate the ability of differential diagnosis of prostate specific antigen decline rate (PSADR) per week, degree of prostatic collapse (DPC) and tissue signal rate of prostate (TSRP) between prostatitis and prostate cancer. The clinical data of 92 patients [prostate specific antigen (PSA) > 10 ng/mL] who underwent prostate biopsy in the Department of Urology, the Second Affiliated Hospital of Xi ’an Jiaotong University from May 2017 to April 2020 were reviewed retrospectively. They were divided into two groups, prostatitis group (n = 42) and prostate cancer (PCa) group (n = 50), according to pathological results. Parameters, like patient characteristics, PSADR, DPC, TSRP and infectious indicators, were compared and analyzed by t test or non-parametric test to identify if there were significant differences. The thresholds of parameters were determined by the receiver operating characteristic curve (ROC), and the data were analyzed to investigate the diagnostic value in distinguishing of prostatitis and prostate cancer. There were statistical differences in age, PSADR, DPC, TSRP, neutrophil percentage in serum, white blood cell (WBC) in urine and prostate volume between prostatitis group and PCa group (P < 0.001, < 0.001, = 0.001, 0.001, 0.024, 0.014, < 0.001 respectively). There was no statistical difference in serum WBC count, serum neutrophil count, monocyte percentage and urine bacterial count between two groups (P = 0.089, 0.087, 0.248, 0.119, respectively). Determined by ROC curve, when the thresholds of PSADR per week as 3.175 ng/mL/week, DPC as 1.113, TSRP as 2.708 were cutoffs of distinguishing prostatitis and prostate cancer. When combining these three indexes to diagnose, the accuracy rate of diagnosis of prostatitis was 78.85%, the accuracy rate of diagnosis of prostate cancer was 97.50%. Univariate analysis suggested that PSADR, DPC and TSRP played an important role in differentiating prostate cancer from prostatitis (P < 0.05), multivariate analysis suggested PSADR > 3.175 might be good indicators when distinguishing prostate disease with prostatitis (OR = 14.305, 95%CI = 3.779 ~ 54.147), while DPC > 1.113 and TSRP > 2.708 might be associated with a higher risk of prostate cancer (OR = 0.151, 95%CI = 0.039 ~ 0.588; OR = 0.012, 95%CI = 0.005 ~ 0.524, respectively). The combination of PSADR per week, DPC, and TSRP might be helpful to distinguish prostate cancer and prostatitis, and can reduce unnecessary invasive and histological procedure.

Abstract Background: Our previous study revealed the chemokine CCL22 and its receptor CCR4 are elevated in cervical cancer (CC) tissues. The present study aimed to investigate the potential role of EZH2-induced epigenetic activation of CCL22/CCR4 and caused EMT remodeling in CC. Methods: We evaluated whether CCL22-CCR4 expression levels could be regulated by EZH2 and subsequently evaluated the mechanism of EZH2 on the CCL22-CCR4. The animal model supported the experimental findings. Results: CCL22 and CCR4 were significant up-regulated in CC samples compared with normal cervix tissues, and obvious induction of promoter DNA methylation levels of CCL22and CCR4 was shown in CC tissues. Demethylation reactivated the transcription of CCL22 and CCR4. DNMT3A was found to directly bind to the CCL22and CCR4 promoter regions in vitro. Downregulation of the expression of EZH2 in CC cell lines altered DNMT3A expression, induced CCL22and CCR4 promoters’ methylation level as well, and decreased CCL22and CCR4 mRNA expression. An in vivo assay showed that, EZH2 regulated the expression of CCL22/CCR4 components through DNMT3A, consistent with the in vitro results. In EZH2-silenced CC cells, migration was reduced, levels of EMT related markers, including vimentin, slug, snail and β-catenin, were all reduced, and ZO-1 increased. In DNMT3A-silenced CC cells, migration was induced and vimentin, slug, snail and β-catenin were all induced, ZO-1 reduced. Inhibition of CCL22 protein significantly decreased migration of CC cells and vimentin, slug, snail and β-catenin, increased ZO-1. Conclusions: Overall, EZH2 thus appears to regulate CCL22/CCR4 expression via epigenetic activation, causing EMT process remodeling in CC progression.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with extremely limited treatment; the effective targeting strategy stays an urgent unmet need. Neuropilin-2 (NRP2), a multifunctional transmembrane non-tyrosine-kinase glycoprotein, enhances various signal transduction pathways to modulate cancer progression. However, the application value of NRP2 as a therapeutic target in pancreatic cancer is still unclear. Here, we detected the elevated NRP2 was associated with the poor prognosis of pancreas carcinoma. The mouse monoclonal antibody targeting NRP2 (N2E4) that could specifically bind to PDAC cells was developed. Moreover, N2E4 inhibits PDAC proliferation, migration, and invasion in vitro, and repressed growth and metastasis in vivo. Mechanistically, the effect of N2E4 was mainly related to the blocking of interaction between NRP2 with integrinβ1 to inhibit FAK/Erk/HIF-1a/VEGF signaling. Therefore, N2E4 has the potential for targeting therapy of PDAC. This study lays a foundation for the future development of NRP2-based targeted therapy for PDAC.

To explore the clinical significance of the perioperative counts of circulating tumor cells (CTCs), mesenchymal CTCs (MCTCs), and CTC- white blood cells (WBCs) in renal cell carcinoma patients. A total of 131 patients with renal cancer who underwent operation excision from our hospital were enrolled. In addition, 20 patients with benign renal diseases were recruited as a control. Blood samples were collected from the 131 patients, before operation and 3 months after surgery. Samples were also obtained simultaneously from the control group. CanPatrol CTC detection technique was used to enrich and identify CTCs, MCTCs, and CTC-WBCs. All enrolled patients were T1-3N0M0. From these, 52 patients with renal cancer underwent radical resection, while other 79 patients underwent nephron-sparing surgery. The positive rate of CTC, MCTC, and CTC-WBC before surgery were 95.4% (125/131), 61.1% (80/131), and 11.5% (15/131), respectively. Preoperative total CTCs, MCTCs, or CTC-WBCs were poorly correlated with patients’ parameters. Preoperative CTC, MCTC, or CTC-WBC showed no association with progression-free survival (PFS). In contrast, postoperative total CTCs (≥6), positive MCTCs, and positive CTC-WBCs significantly correlated with recurrence and metastasis. These results remained independent indicators for worse PFS. In addition, the increased CTC and MCTC count after surgery also correlated with unfavorable PFS. The detection of six or more total CTCs, MCTC, or CTC-WBCs in peripheral blood after surgery might help to identify a subset of patients that have higher recurrent risk than the overall population of patients with at different stages of renal cancer.

目的:检测免疫抑制细胞Foxp3+Treg和免疫蛋白IDO在不同病变宫颈组织中的表达情况.方法:采用免疫细胞化学及蛋白印记(Western blot)检测Foxp3蛋白及IDO蛋白在宫颈癌细胞系HeLa、SiHa及C33A中的表达与分布;采用免疫组织化学法检测Foxp3和IDO在20例正常宫颈组织及45例不同程度宫颈病变组织中的表达情况.结果:Foxp3蛋白在HeLa、SiHa及C33A中无表达;IDO蛋白在HeLa、SiHa及C33A细胞的胞浆中均有表达.Foxp3蛋白在宫颈组织中表达于Treg,IDO蛋白在宫颈组织中表达于APC和/或异常细胞.宫颈病变组织中的Foxp3+Treg(H=43.211,P=0.000)和IDO蛋白的表达均明显高于正常组织(χ2=20.028,P=0.00;Z=226.600,P=0.00).随着病理级别升高,Foxp3+Treg的侵袭性(H=28.307,P=0.000)增加,Foxp3+Treg与IDO+APC的数目显著正相关(rs=0.550,P=0.003)统计学正相关(rs=0.550,P=0.000).结论:在宫颈癌进展的不同病理阶段,局部微环境中Foxp3+Treg数目随宫颈细胞恶性转化的进程而增多,IDO+APC细胞在早期宫颈病变组织中表达多于晚期病变.

As a new kind of RNA, circular RNA (circRNA) is a endogenous non-coding RNA with circular structure, which has the characteristics of universality, stability, conservatism and specificity. CircRNA can specifically bind to microRNAs (miRNAs) in the form of competitive endogenous RNA, thus directly or indirectly regulating the expression of related genes. In addition to the role of sponge, circRNA also regulates parental gene expression, transcriptional translation and protein modification; and it can be used as a biomarker to develop potential diagnosis and treatment methods and evaluate prognosis. Due to changes in dietary habits and genetic factors, the morbidity and mortality of esophageal cancer (EC) in the world are still high, and are prone to early metastasis. Although the diagnosis and treatment techniques have been improved in recent years, the early diagnosis of EC is not common, and the 5-year survival rate of patients is still very low. This article reviews the function and significance of circRNA and discusses the research progress of circRNA as biomarkers in EC.

Purpose: PARP inhibitors are a novel targeted anti-cancer drug and a large number of clinical studies on PARP inhibitors have been accomplished. This updated meta-analysis was conducted to evaluate the efficacy and safety of PARP inhibitors in advanced-stage epithelial ovarian cancer. Methods: Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to identify the eligible trials up to April 2020. ClinicalTrials.gov was also screened for additional unpublished trials. Data extraction and risk of bias assessment were performed by two independent investigators, respectively. The hazard ratios (HRs) and its 95% confidence intervals (CI) for time-to-event data of progression-free survival (PFS) and overall survival (OS), and the risk ratios (RRs) with 95% CI for dichotomous data of overall response rate (ORR) and occurrence of adverse events (AEs) were calculated by Review Manager 5.3 and Stata 12.0 software. Results: A total of 12 trials with 5,347 patients were included in this meta-analysis. Compared with the control group, PARP inhibitors significantly improved PFS (HR, 0.51; 95% CI, 0.40-0.65; P < 0.00001) and ORR (RR, 1.26; 95% CI, 1.11-1.43; P = 0.0003). Specifically, PFS was improved regardless of BRCA genes mutations and homologous-recombination status. However, no difference was observed in OS between the PARP inhibitors group and the control group (95% CI, 0.73-1.01; P = 0.06). PARP inhibitors were associated with a statistically significant higher risk of hematologic events and different PARP inhibitors had different toxicities profiles. Conclusion: PARP inhibitors are an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer.

Lung carcinoma is a prominent cause of mortality among patients with cancer. Previous studies have reported the vital role of long non-coding RNAs (lncRNAs) in the malignant progression of lung cancer. lncRNA RP11-284F21.9 was originally identified to be expressed in lung carcinoma, but its specific function remains unknown. Therefore, the present study aimed to elucidate the role of lncRNA RP11-284F21.9 in lung carcinoma progression. The expression of RP11-284F21.9 in lung cell lines and tissues was measured using reverse transcription-quantitative PCR. The endogenous expression of RP11-284F21.9 was silenced using RNA interference, and cell viabilities were measured with a Cell Counting Kit-8 assay. The invasion and apoptosis of cells were determined via Transwell assays and flow cytometry, respectively. The protein expression levels were measured by western blotting. An increased expression of RP11-284F21.9 was identified in both lung carcinoma tissues and cells. Knockdown of RP11-284F21.9 in lung carcinoma cells inhibited cell proliferation and invasion, but promoted cell apoptosis. The present study identified the existence of a direct interaction between RP11-284F21.9 and microRNA (miRNA/miR)-627-3p. Mechanistically, it was demonstrated that RP11-284F21.9 promoted the proliferation and invasiveness of lung carcinoma cells, in part, via the regulation of miR-627-3p. Furthermore, cell division cycle and apoptosis regulator 1 (CCAR1) was identified as a target gene of miR-627-3p. The in vivo tumor growth assay also demonstrated that the knockdown of RP11-284F21.9 suppressed tumor growth, upregulated miR-627-3p and downregulated CCAR1 in the xenograft model of nude mice. Thus, the present findings indicated the tumor promoting functions of RP11-284F21.9 in the progression of lung carcinoma, and provided a novel lncRNA/miRNA axis as a target for the management of lung cancer.

Objective Micro RNA (miR)-363 has many important biological functions in cancers, but its roles in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods We used reverse transcription PCR to quantify the expression of miR-363 in 80 ESCC tissues and analyzed its relationship with clinicopathological factors and overall survival. The effects of miR-363 on cell proliferation, apoptosis, and invasion were detected using the MTT assay, flow cytometry, and Transwell invasion assays, respectively. Further, we investigated the post-transcriptional regulation of sperm-associated antigen 5 (SPAG5) expression by miR-363 using luciferase reporter assays. Finally, the effects of SPAG5 on miR-363 were studied by SPAG5 overexpression. Results miR-363 expression was decreased in both ESCC specimens and cell lines, compared with controls, and correlated with lymph node metastasis and tumor differentiation. Low miR-363 expression was identified as an independent prognostic factor for ESCC. miR-363 overexpression decreased ESCC cell proliferation and invasion and increased apoptosis, while the opposite was seen after miR-363 inhibition. Moreover, SPAG5 was identified as a direct target of miR-363, and the reintroduction of SPAG5 restored miR-363-induced effects. Conclusions miR-363 acts as a tumor suppressor by post-transcriptionally regulating SPAG5 expression, suggesting its potential as a diagnostic biomarker and therapeutic target for ESCC.