Background The role of ubiquitination modification in colorectal cancer (CRC) has been increasingly recognized. The study was designed to explore key ubiquitination-related genes and their underlying mechanisms in CRC through bioinformatics analysis and experimental validation. Methods Data were obtained from public databases, and ubiquitination-related candidate genes were recognized through differential expression, intersection analyses, univariate Cox regression, and expression trend matching. Subsequently, these genes were ascertained via RT-qPCR in cell lines to identify the key ubiquitination-related gene that has not yet been reported in CRC. The prognostic value and biological functions of the key gene were assessed by survival analysis and enrichment analysis. Finally, a series of in vitro functional assays—such as cell counting kit-8, wound healing, Transwell migration, and co-immunoprecipitation—were performed to explore the molecular mechanisms of the key gene in CRC. Results ANKRD13D was markedly elevated in CRC tissues and cell lines, and its high expression was notably connected with bad prognosis in patients, identifying it as a key ubiquitination-related gene. Enrichment analysis unveiled that ANKRD13D was participated in oxidative phosphorylation and the notch signaling pathway. Functionally, knockdown of ANKRD13D impeded CRC cell proliferation, migration, and invasion. Mechanistically, ANKRD13D was shown to interact with p-ERK protein, enhancing its stability and thereby activating the MAPK signaling pathway. Conclusion ANKRD13D, as a novel prognostic biomarker for CRC, regulates the MAPK signaling pathway by stabilizing p-ERK, suggesting its potential as a therapeutic target.

Resistance to 5-fluorouracil (5-FU) remains a major clinical challenge in colorectal cancer (CRC) treatment. This study investigates the non-canonical role of ribonucleotide reductase subunit M1 (RRM1) in regulating autophagy-mediated chemoresistance. A comprehensive multi-omics strategy, including metabolomics, transcriptomics and proteomics analyses, was employed to study 5-fluorouracil-resistant colorectal cancer tissues from patients and matched drug-resistant cell models. Protein-protein interactions, ubiquitination events and functional consequences were validated via complementary assays including Co-IP, GST pull-down, in vivo ubiquitination, structure-guided molecular docking, site-directed mutagenesis, and subcutaneous xenograft mouse models. Structure-based virtual screening was conducted to identify candidate compounds targeting the RRM1-USP19 interaction, with in vivo anti-tumor activity verified in 5-FU-resistant CRC xenografts. RRM1 is significantly downregulated in 5-FU-resistant CRC tissues, and low RRM1 expression correlates with poor clinical prognosis. Mechanistically, RRM1 directly binds USP19 via conserved E647/R648 residues, competitively blocking NEDD4-mediated USP19 K387 ubiquitination and subsequent proteasomal degradation. Loss of RRM1 destabilizes USP19, impairs autophagic substrate deubiquitination, hyperactivates autophagic flux and thereby induces 5-FU resistance. Restoration of RRM1 or expression of the ubiquitination-defective USP19-K387R mutant re-sensitizes resistant CRC cells to 5-FU. The peptide GAGGVGKSAL, identified via virtual screening, specifically disrupts the RRM1-USP19 interface, inhibits excessive autophagy and potently suppresses tumor progression in 5-FU-resistant CRC xenograft models. This study identifies the novel RRM1-USP19-NEDD4 regulatory axis as a core mediator of autophagy-driven 5-FU resistance in CRC, uncovers a non-canonical, metabolism-independent role of RRM1 as a USP19 stabilizer via competitive inhibition of NEDD4-mediated ubiquitination, and validates GAGGVGKSAL as a promising lead compound targeting this axis to reverse 5-FU resistance. The RRM1-USP19-NEDD4 axis represents a novel therapeutic target for overcoming chemoresistance in CRC.

Colorectal cancer (CRC) urgently requires mechanism-driven therapeutic strategies. Nomilin, a natural limonoid with established anticancer properties, lacks well-defined molecular targets in CRC. Integrated in vitro and in vivo analyses demonstrated that Nomilin suppressed CRC proliferation in a dose-dependent manner, concomitant with significant downregulation of the proliferation markers PCNA and Ki67. Leveraging network pharmacology and molecular docking, we identified HSP90AA1 as a high-affinity direct binding target of Nomilin. Mechanistically, Nomilin promoted ubiquitination and subsequent proteasomal degradation of HSP90AA1, leading to sustained inhibition of the PI3K/AKT signaling axis. This inhibition triggered ferroptosis, an iron-dependent form of regulated cell death characterized by lethal accumulation of lipid peroxides, as evidenced by glutathione (GSH) depletion, elevated intracellular Fe2+, malondialdehyde (MDA), and lipid reactive oxygen species (ROS); mitochondrial shrinkage and increased membrane density; and dysregulation of core ferroptosis regulator. Crucially, forced overexpression of HSP90AA1 abolished Nomilin-induced ferroptosis and PI3K/AKT suppression, whereas co-treatment with the PI3K inhibitor LY294002 phenocopied Nomilin’s effects. Furthermore, ferroptosis-specific inhibitors fully rescued CRC cells from Nomilin-induced death. Collectively, our findings establish that Nomilin exerts antitumor effects in CRC by directly targeting HSP90AA1, inducing its ubiquitin–proteasome–mediated degradation, inhibiting PI3K/AKT signaling, and consequently activating ferroptosis.

Bifenthrin (BF) is a widely used pyrethroid insecticide and is recognized as an endocrine-disrupting chemical (EDC). Accumulating evidence indicates that long-term exposure to BF can induce a variety of adverse health outcomes. However, its potential role in the pathogenesis of ulcerative colitis (UC) remains elusive. In this study, we integrated data from multiple databases—including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH—to predict potential molecular targets of BF. UC-associated genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), DisGeNET, Therapeutic Target Database (TTD), and DrugBank. Candidate targets were identified by intersecting predicted BF targets with UC-related genes, followed by functional enrichment analysis using DAVID. The STRING database and Cytoscape software were employed to construct protein-protein interaction (PPI) networks and screen for hub genes. A diagnostic model based on these hub genes was established and validated using the GSE47908 and GSE13367 datasets. Additionally, immune infiltration analysis was performed to compare the UC group with controls, identifying immune cell types significantly associated with the target genes. Molecular docking simulations via AutoDock Vina were conducted to evaluate the binding affinities between BF and the five hub proteins. Functional analysis revealed that the candidate genes were primarily enriched in pathways related to oxidative stress and inflammatory responses. Five core hub genes—BCL2, TP53, TNF, IL6, and PTGS2—were consistently identified across all analytical platforms. In vitro experiments demonstrated that BF exposure significantly exacerbated colonic inflammation by downregulating anti-inflammatory/apoptotic genes (BCL2, TP53) and upregulating pro-inflammatory markers (IL6, TNF, PTGS2). Collectively, our findings suggest that bifenthrin may promote colorectal inflammation by dysregulating key genes and modulation of the pro-inflammatory immune microenvironment, thus providing novel insights into the environmental etiology of UC.

The tetraspanins are closely associated with the development and therapeutic prognosis of colorectal tumors. These proteins play a role in cell proliferation, metastasis, and invasion, regulate apoptosis and autophagy of colorectal tumor cells. affect immune escape by releasing exosomes, intervening the epithelial-mesenchymal transition process, and altering the tumor microenvironment, and enhance tumor stemness through specific pathways. This paper reviews the mechanisms and current research regarding the status of tetraspanins in colorectal cancer, aiming to improve early diagnosis and providing valuable insights for treatment strategies.

BACKGROUND Among all forms of heterotopic ossification, heterotopic mesenteric ossification (HMO) is rare, with fewer than 100 reported cases to date. Postoperative early small bowel obstruction caused by HMO is even rarer, presenting extremely high surgical risks, the potential for multiple surgeries, and a poor prognosis. There have been no reported cases of conservative treatment for resolving such early postoperative obstruction. CASE SUMMARY A 57-year-old male presented with severe postoperative small bowel obstruction shortly after undergoing open radical resection for transverse colon cancer. Laparotomy revealed extensive adhesions in the proximal jejunum and mesentery, making it too difficult to relieve without injuring the small bowel. Additionally, multiple fixed nodules were found in the mesentery during the operation. Pathology confirmed the presence of heterotopic ossification. The patient was treated with methylprednisolone on postoperative day 1, which gradually relieved his symptoms. CONCLUSION Hormone therapy may have a potential role in treating small bowel obstruction caused by early HMO after operative intervention.

Colorectal cancer metastasis remains a major cause of cancer-related mortality, with the Metastasis-Associated in Colon Cancer 1 (MACC1) protein emerging as a critical regulator of tumor progression. Although exosomes are recognized mediators of oncogenic communication, the interplay between MACC1 and exosome biology is yet to be fully explored. This study unveils a dual mechanism through which MACC1 coordinates exosome biogenesis and oncogenic cargo delivery to drive metastatic progression.We first established clinical relevance by Pearson's demonstrating a significant correlation between MACC1 expression and exosome concentration in colorectal tumors (r = 0.457, P < 0.05). Functional studies showed that MACC1-overexpressing HCT116 cells exhibited enhanced invasiveness and transmitted pro-metastatic signals via exosomes. These exosomes were significantly enriched in the c-Met oncoprotein (P < 0.05 vs. controls) and could induce epithelial-mesenchymal transition in recipient SW480 cells, significantly enhancing their migration and invasion capacities.Mechanistically, transcriptomic analysis identified several components of the exosome secretion machinery (YKT6, RAB22A, and VPS41) as downstream targets of MACC1. Promoter-binding assays confirmed that MACC1 directly activates the transcription of YKT6, a member of the Soluble N-ethylmaleimide-sensitive factor attachment protein receptor family. This protein is critical for multivesicular body-plasma membrane fusion. The transcriptional activation led to cytoplasmic accumulation of YKT6 (P < 0.05), driving a 2.9-fold increase in exosome secretion. Crucially, YKT6-mediated exosome hypersecretion facilitated the extracellular release of c-Met-enriched vesicles, establishing a feed-forward loop for metastatic propagation.Our findings delineate an integrated metastatic axis: MACC1 orchestrates (1) transcriptional upregulation of YKT6 to amplify exosome production, and (2) selective packaging of c-Met into exosomes that prime recipient cells for invasion. This dual regulatory mechanism highlights potential therapeutic targets for intercepting metastasis-specific exosome signaling in colorectal cancer.

Oogenesis is an energy-intensive process critical for reproductive success. To ensure proper coordination with developmental stages and nutritional status, complex regulatory mechanisms have evolved. Using C. elegans previous studies have emphasized the role of hypodermis and intestinal cells—key tissues that sense developmental status and environmental nutrition—as major regulators of oogenesis and reproduction, while whether and how neurons also play a role in regulating oogenesis is not well studied. In this study, we found that a neuron derived signaling pathway, Netrin-1/UNC-6 and its receptors DCC/UNC-40 and UNC-5 regulates germ cell apoptosis. Our results indicate that Deleted in Colorectal Cancer, DCC/UNC-40 differently regulate germ cell apoptosis depending on the presence of its ligand Netrin-1/UNC-6. Loss-of DCC/UNC-40 promotes apoptosis in the presence of Netrin-1/UNC-6, while inhibits apoptosis in the absence of Netrin-1/UNC-6. The alternative receptor of Netrin-1/UNC-6, UNC-5 compensates for the loss-of DCC/UNC-40, and partially explains for the opposite effect of DCC/UNC-40 in regulating apoptosis, dependent on its ligand Netrin-1/UNC-6. Our results revealed a potential compensation mechanism of the controversial function of DCC/UNC-40 on regulating apoptosis, as well as colorectal cancer development, and thus provided a potential therapy for colorectal cancer by synthetically targeting DCC/UNC-40 with its ligand Netrin-1/UNC-6, or with its competitive Netrin-1/UNC-6 receptor UNC-5.

As the primary active component of chili peppers, capsaicin (CAP) remains controversial regarding its potential carcinogenic effects. This study aimed to elucidate the role of capsaicin in tumor progression and its underlying molecular mechanisms. Cellular proliferation was assessed using MTT assay and soft-agar colony formation assay. Mitochondrial morphology was observed via transmission electron microscopy (TEM), while untargeted metabolomics and proteomics were combined to identify key targets. Molecular docking, cellular thermal shift assay (CETSA), and ACSL4 point mutant plasmid validation were employed to investigate mechanistic interactions. Results demonstrated that capsaicin inhibits ferroptosis by promoting ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4). Molecular docking and coimmunoprecipitation-mass spectrometry (Co-IP/MS) revealed that capsaicin and the E3 ubiquitin ligase SYVN1 synergistically target ACSL4. Key site mutation experiments confirmed that capsaicin directly binds to the Asp362 residue of ACSL4, enhancing its interaction with SYVN1. This promotes SYVN1-mediated polyubiquitination of ACSL4 at Lys367, ultimately suppressing ferroptosis and accelerating tumor progression. This study is the first to elucidate capsaicin's novel mechanism of antagonizing ferroptosis by regulating ACSL4 degradation via the ubiquitin-proteasome system. These findings provide a theoretical foundation for dietary interventions for colorectal cancer (CRC) patients.

BackgroundChronic Liver Disease (CLD) is one of the frequent causes of death, especially in the developing world. Liver transplantation (LT) is an effective modality to treat end-stage liver disease. Perioperative management of liver transplantation patients and prevention of postoperative complications are the key to improving patient prognosis and quality of life, and the intestinal flora of these patients can affect postoperative complications and overall prognosis.MethodWe collected a total of 151 fecal samples from 59 liver transplantation patients at different stages from the First Hospital of Shanxi Medical University. Using 16S rRNA sequencing technology, we compared the characteristics and changes of their microbiota. We selected 42 samples for metagenomic sequencing using the microPITA method to further analyze the composition and functional differences of the microbiota during the perioperative period of liver transplantation across various time points.ResultsAfter liver transplantation (LT), the diversity of gut microbiota initially decreased and then increased. Firmicutes, Proteobacteria, and Bacteroidota were the main bacterial groups during the perioperative period. Firmicutes and Proteobacteria initially decreased and then increased, while Bacteroidota exhibited the opposite process. Alpha diversity and beta diversity analyses indicated that 1 month post-transplantation was a turning point for microbiota recovery (P < 0.01). Metagenomic sequencing, analyzed using the LEfSe method, identified a total of 50 genera that played significant roles in this process. The changes in microbiota exhibited the same trend as the 16S rRNA results. KEGG pathway analysis also indicated that 1 month was a critical time point, with Ko02010 potentially being a key pathway for recovery in LT patients, and it showed a negative correlation with Bacteroidota (P < 0.05).ConclusionThe diversity of intestinal flora in the perioperative period of LT patients decreased first and then increased, and the turning point of intestinal flora recovery was 1 month after LT surgery.

OBJECTIVE:Perfluorooctanesulfonic acid (PFOS), a persistent environmental pollutant, is implicated in immune dysregulation. Rising inflammatory bowel disease (IBD) incidence parallels environmental contamination, yet PFOS's role in gut inflammation remains unclear. Its immunotoxicity may disrupt intestinal homeostasis via barrier dysfunction or cytokine imbalance, but molecular targets and pathways linking PFOS to IBD pathogenesis require elucidation to inform risk mitigation strategies. METHODS:This study aims to elucidate the mechanism of action of PFOS in the development and progression of IBD. Additionally, relevant PFOS targets and IBD-associated genes were screened using databases such as results indicate that PFOS is significantly associated with key pathways involved in IBD, and it can specifically bind to crucial IBD proteins like albumin, epidermal growth factor, fos proto-oncogene, and interleukin-10. RESULTS:The study suggests that PFOS may contribute to the pathogenesis of IBD by interfering with key proteins and signaling pathways, highlighting its potential health risks, and providing a theoretical basis for subsequent clinical research and prevention strategies. CONCLUSION:In conclusion, this study has untangled the potential mechanistic link between PFOS exposure and inflammatory bowel disease, offering a novel perspective for environmental health science and public health policies and profound implications.

Purpose: Thymidylate synthase (TYMS) is a key regulatory enzyme in DNA synthesis. We identified the biological effect and molecular mechanisms of TYMS in colorectal cancer (CRC). Methods: We employed western blot and immunohistochemistry for the assessment of TYMS expression in CRC samples. MTT and colony assay were carried out to illuminate the effect of TYMS on the proliferation of CRC cells. Xenograft models were constructed to evaluate the consequences of TYMS overexpression on CRC in vivo. Metabolomics was utilized to analyze the alterations in cellular molecular metabolites subsequent to TYMS overexpression. The impact of TYMS on NRF2 localization and KEAP1 expression was explored by means of western blot. The expression levels of GSH, ROS, MDA, and PTGS2 mRNA were measured to assess ferroptosis. Results: TYMS expression in CRC tumor tissues was upregulated compared to adjacent non-cancerous tissues. Cells overexpressing TYMS displayed enhanced proliferative capabilities. Metabolomic analysis revealed that overexpression of TYMS was associated with elevated levels of GSH within cells and a decrease in the lipid peroxidation product, 4-hydroxyhexenal. ROS detection assays further demonstrated a significant enhancement in cellular antioxidant capacity due to TYMS overexpression. Overexpression of TYMS downregulated KEAP1 expression and promoted NRF2 translocation into the nucleus. Consequently, transcription of downstream antioxidant genes was upregulated, enhancing cellular antioxidant capacity, reducing ROS levels, diminishing lipid peroxidation products, and heightening resistance to ferroptosis induced by erastin. Additionally, our study indicated that the TYMS inhibitor 5-fluorouracil (5-FU) exhibited favorable drug synergism with erastin. Conclusion: TYMS was overexpressed in CRC, which was correlated with poor prognosis of CRC patients. TYMS enhanced the antioxidant capacity of CRC cells via the KEAP1-NRF2 pathway, thereby increasing resistance to erastin-induced ferroptosis.

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, which has a high mortality rate especially for patients with CRC recurrence. However, the pathological mechanism of recurrence of CRC is unclear. In this study, we integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in recurrence of CRC. As results, 628 DEGs were identified from GSE33113 and GSE2630 datasets and their function and pathway were analyzed. 14 hub genes related to CRC recurrence were screened from and their influence on survival were analyzed. Two key genes (IL1B and DDAH1) regarded as prognostic factors were further screened. Relapse-free survival results indicated the interaction between IL1B and DDAH1 genes and B cells was the most obvious and correlated with survival, with statistical significance (P <0.05). Specially, cox regression analysis suggested that patients with T1 and N0 stages had a higher risk of recurrence than patients with T2 and N1. This work would provide potential value for prognosis, and would promote molecular targeting therapy for CRC recurrence.

Dihydroorotate dehydrogenase(DHODH)is a flavin-dependent metabolic enzyme that oxidizes dihydroorotate acid to orotic acid in the de novo synthesis pathway of pyrimidine metabolism.DHODH is located in mitochondria,closely related to cellular oxidative phosphorylation,and an important suppressor of the ferroptosis pathway.This study investigates the influence of DHODH on the progression of malignant tumors,including its important role in the de novo synthesis of pyrimidine,oxidative phosphorylation,and ferroptosis.The objective is to present evidence that DHODH is a potential target for the clinical treatment of tumors.

Ferroptosis therapy has emerged as a promising strategy for cancer treatment due to its unique cell death mechanism and tumor targeting. However, for colorectal cancer (CRC), the tumor cells exhibit ferroptosis resistance, and the reason remains a debate. To enhance the ferroptosis activity for CRC treatment, herein, we loaded a Co single-atom nanozyme on the Fe-based zeolitic imidazolate framework (ZIF) via atomic layer deposition. The synthesized materials performed better anti-HT29 tumor activity in vitro and in vivo than Fe-based ZIFs and showed excellent biosecurity. Based on bioinformatics analysis, Western blot, and immunohistochemical analyses, it was found that the catalyst not only increased the reactive oxygen species by consuming glutathione via the GPX4 pathway but also downregulated the JAK1-STAT3 signal pathway, which benefited to reduce the ferroptosis resistance. This work provides an innovative strategy for CRC treatment and highlights the function of single-atom nanozymes in reducing the ferroptosis resistance.

Thymosin beta 10 (TMSB10) overexpression is a general characteristic in human carcinogenesis. It is involved in the malignant process of generating multiple cancers. However, there are only a few reports about TMSB10 in colorectal cancer (CRC) and the mechanism of its carcinogenetic effect is still poorly understood. The present study intends to clarify the biological roles and carcinogenic mechanism of TMSB10 in CRC and to explore the possibility whether TMSB10 might be useful as a non-invasive serum tumor biomarker in detecting CRC. Immunohistochemical results showed that TMSB10 protein expression in CRC tissues was generally higher than that in adjacent tissues, and the TMSB10 contents in serum of CRC patients was significantly elevated compared to that of healthy controls. Knockdown-TMSB10 increased apoptosis and induced S-cell cycle arrest, and finally inhibited cell proliferation in vitro and in vivo. Transcriptome sequencing and western blotting analysis revealed that knockdown-TMSB10 increased phosphorylation of p38 and activated the p38 pathway that blocked cell cycle and promoted apoptosis. Taken together, our study indicated that TMSB10 could serve as a minimally invasive serum tumor marker in detecting CRC. At the same time it demonstrates an effective regulatory capacity of TMSB10 on cell proliferation of CRC, suggesting that TMSB10 and downstream effector molecules regulated by TMSB10 could further be applied as an appealing target in clinical post-surgery chemotherapy.

BackgroundCuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC.MethodsFirst, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan-Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model.ResultLasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan-Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR.ConclusionThe signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.

结直肠癌主要是起源于结直肠表面黏膜上皮细胞的腺癌,已成为第四大最常见和第三大最致命的恶性肿瘤.手术切除是结直肠癌的主要治疗方法,放疗和化疗是晚期结直肠癌转移病人的治疗策略,此外,细胞治疗、基因治疗、免疫治疗和靶向治疗在结直肠癌治疗中也表现出了突出的潜力.然而,上述策略由于存在转移复发、系统毒性、多机制耐药、非特异性强和获益人群有限等问题,应用局限.因此有必要探索一种新的非侵入性、对肿瘤细胞具有高度选择性和对正常组织最小毒性的治疗策略来应对这些挑战.光动力疗法联合纳米材料作为一种治疗结直肠癌的新手段,有望克服这些挑战.该研究综述了光动力疗法的原理及纳米颗粒在结直肠癌光动力疗法中的应用,以期为科研与临床提供一种思路.

Purpose Colorectal cancer is a common malignant tumor worldwide. In China, the ratio of rectal cancer to colon cancer in terms of incidence is close to 1: 1. Low rectal cancer accounts for more than half of all cases of rectal cancer. In recent years, the proportion of rectal cancer has trended downward, however the incidence of rectal cancer in younger adults is increasing. The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal Cancer Society, based on a careful review of the latest evidence including China’s studies, and referred to domestic and international relative guidelines, also considered China’s specific national conditions and clinical practice. Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectal cancer, prevention and screening, diagnosis, treatment of nonmetastatic and metastatic rectal cancer, follow-up, and whole-course rehabilitation management. Conclusion Committee of Colorectal Cancer Society, Chinese Anti-Cancer Association, standardizes the diagnosis and treatment of rectal cancer in China through the formulation of the CACA Guidelines.

MicroRNA-328-3p (miR-328-3p) plays a critical role in mediating the progression of multiple types of cancers. To date, no study has concentrated on the molecular mechanism of miR-328-3p in mediating stomach adenocarcinoma (STAD). In this study, it was found that miR-328-3p was downregulated in STAD, and inhibition of miR-328-3p significantly promoted the growth, migration, invasion, and stemness of STAD cells, while miR-328-3p overexpression exerted reverse effects. Through bioinformatics analysis, it was uncovered that a cluster of differentiation 44 (CD44) was upregulated in STAD and closely associated with the prognosis of STAD patients. Mechanistically, we identified CD44 as the target gene of miR-328-3p. Notably, knockdown of CD44 abolished the promoting function of miR-328-3p inhibitor in the development of STAD. Moreover, myeloid zinc finger protein 1 (MZF1) was confirmed as an upstream transcription factor for miR-328-3p, which is involved in enhancing miR-328-3p expression. In addition, the role of MZF1 downregulation in the malignant traits of STAD cells was blocked by miR-328-3p overexpression. More importantly, upregulation of miR-328-3p efficiently suppressed STAD tumor growth in vivo. Collectively, our findings illustrated that MZF1-mediated miR-328-3p acted as a cancer suppressor in STAD progression via regulation of CD44, which suggested the possibility of the MZF1/miR-328-3p/CD44 axis as a novel promising therapeutic candidate for STAD.