Colorectal cancer (CRC) is one of the most prevalent and deadliest illnesses all around the world. Growing proofs demonstrate that tumor-associated macrophages (TAMs) are of critical importance in CRC pathogenesis, but their mechanisms remain yet unknown. The current research was designed to recognize underlying biomarkers associated with TAMs in CRC. We screened macrophage-related gene modules through WGCNA, selected hub genes utilizing the LASSO algorithm and COX regression, and established a model. External validation was performed by expression analysis using datasets GSE14333, GSE74602, and GSE87211. After validating the bioinformatics results using real-time quantitative reverse transcription PCR, we identified SPP1, C5AR1, MMP3, TIMP1, ADAM8 as potential biomarkers associated with macrophages in CRC.

The vaginal microbiome (VM) is associated with human papillomavirus (HPV) infection and progression, but a thorough understanding of the relation between HPV infection, and VM needs to be elucidated. From August to December 2022, women who underwent routine gynecological examinations were screened for HPV infection. The distribution of HPV variants and clinical characteristics were collected. Then, a total of 185 participants were enrolled and divided into HPV-negative (HC), high-risk HPV (H), low-risk HPV (L), multiple high-risk HPV (HH), and mixed high-low risk HPV (HL) groups. Samples were collected from the mid-vagina of these 185 participants and sent for 16S rDNA sequencing (V3–V4 region). Among 712 HPV-positive women, the top 3 most frequently detected genotypes were HPV52, HPV58, and HPV16. Among 185 participants in the microbiology study, the β diversity of the HC group was significantly different from HPV-positive groups ( P < 0.001). LEfSe analysis showed that Lactobacillus iners was a potential biomarker for H group, while Lactobacillus crispatus was for L group. Regarding HPV-positive patients, the α diversity of cervical lesion patients was remarkably lower than those with normal cervix ( P < 0.05). Differential abundance analysis showed that Lactobacillus jensenii significantly reduced in cervical lesion patients ( P < 0.001). Further community state type (CST) clustering displayed that CST IV was more common than other types in HC group ( P < 0.05), while CST I was higher than CST IV in H group ( P < 0.05). Different HPV infections had distinct vaginal microbiome features. HPV infection might lead to the imbalance of Lactobacillus spp. and cause cervical lesions. IMPORTANCE: In this study, we first investigated the prevalence of different HPV genotypes in south China, which could provide more information for HPV vaccinations. Then, a total of 185 subjects were selected from HPV-negative, high-risk, low-risk, multiple hr-hr HPV infection, and mixed hr-lr HPV infection populations to explore the vaginal microbiome changes. This study displayed that HPV52, HPV58, and HPV16 were the most prevalent high-risk variants in south China. In addition, high-risk HPV infection was featured by Lactobacillus iners , while low-risk HPV infection was by Lactobacillus crispatus . Further sub-group analysis showed that Lactobacillus jensenii was significantly reduced in patients with cervical lesions. Finally, CST clustering showed that CST IV was the most common type in HC group, while CST I accounted the most in H group. In a word, this study for the first time systemically profiled vaginal microbiome of different HPV infections, which may add bricks to current knowledge on HPV infection and lay the foundation for novel treatment/prevention development.

Investigate ADAM17 expression in colorectal cancer (CRC) at molecular and cellular levels and its potential mechanism in promoting tumorigenesis by regulating CRC cell migration and invasion. The study measured ADAM17 mRNA and protein levels in colorectal cancer cells and tissues using qPCR and immunohistochemical staining, and assessed the cells' proliferation, migration, and invasion abilities. ADAM17 expression was significantly higher in CRC tissues than in non-cancerous tissues and was linked to metastasis and poor prognosis in CRC patients. Silencing ADAM17 reduced cell migration and invasion. Mechanistically, knocking down ADAM17 decreased the expression of TGF-β/Smad pathway-related proteins, which inhibited proteins associated with migration and invasion, thus impairing these cellular processes. ADAM17 likely promotes the migration and invasion of CRC cells by regulating the TGF-β/Smad signaling pathway. This study aids in understanding the molecular mechanisms of CRC metastasis and development, and supports the development of new therapeutic targets.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Dysregulated small nucleolar RNAs (snoRNAs) have recently been demonstrated to participate in cancer activity through their influence on cellular transformation and carcinogenesis. Specifically, SNORD93 exhibits consistent dysregulation across multiple malignancies and demonstrates significant correlation with adverse clinical outcomes, but it remains unclear how SNORD93 is involved in the development of CRC. In this study, we examined the role of SNORD93 in CRC pathogenesis in order to provide novel diagnostic and treatment targets for CRC. Methods: The expression levels of SNORD93 were quantified in CRC tissue samples (n=13) and paired adjacent normal tissue samples (n=13) from the same patients, as well as in human CRC cell lines (HT-29, SW480, and HCT-15) and the normal human intestinal epithelial crypt cell (HIEC) line via quantitative real-time polymerase chain reaction (qRT-PCR). The biological significance of SNORD93 in the proliferation, migration, cell cycle progression, and cell apoptosis was examined through gain-of-function analyses via Cell Counting Kit-8 (CCK-8) assay, colony formation assay, wound healing assay, and flow cytometry. Additionally, the expression of related proteins was quantified through Western blotting (WB). Results: A significant downregulation of SNORD93 was identified in CRC tissues and cells. Moreover, downregulation of SNORD93 was significantly associated with the poor survival of patients with CRC. In contrast, the overexpression of SNORD93 suppressed the growth of CRC cells in vitro but did not affect CRC cell migration. In terms of mechanism, SNORD93 inhibited cellular proliferation by arresting cells at the G1/S transition phase, while simultaneously inducing apoptosis. Moreover, SNORD93 overexpression correlated with elevated phosphorylation of both receptor-interacting protein (RIP) and mixed lineage kinase domain-like protein (MLKL), suggesting potential involvement of necroptosis pathways. Conclusions: Collectively, these results establish SNORD93 as a functionally significant tumor-suppressive snoRNA in CRC.

Background Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Recently, mounting evidence has identified dysregulated snoRNAs active in cancer by influencing cell transformation and carcinogenesis, and meanwhile, SNORD93 is abnormally expressed and associated with poor prognosis in many cancers. Thus, the present study aimed to investigate the function of SNORD93 in CRC. Methods The expression levels of SNORD93 were measured in CRC tissues and cells by qRT-PCR. Then, the biological significance of SNORD93 on proliferation, migration, cell cycle, and cell apoptosis with gain function analyses was explored by CCK8, colony formation, wound healing, and flow cytometry. Additionally, The expression of related proteins was quantified through Western blotting. Result A significant downregulation of SNORD93 was identified in CRC tissues and cells. Simultaneously, downregulated SNORD93 was considerably associated with poor survival of CRC patients. Furthermore, the overexpression of SNORD93 suppressed CRC cell proliferation via inducing G0/G1 cell cycle arrest and apoptosis, while it didn’t affect CRC cell migration. Conclusion SNORD93 functions as a significant tumor suppressor snoRNA in CRC.

The aryl hydrocarbon receptor (AhR) plays a pivotal role in tumorigenesis; however, its role in cervical cancer is unclear. This study investigated the function of AhR in cervical cancer by analyzing AhR mRNA expression in tumors and adjacent normal tissues from patients and cervical cancer cell lines using RT-qPCR. AhR was overexpressed in cervical cancer cell lines using lentiviral vectors, and its effects on cell viability, colony formation, cell cycle, apoptosis, and migration/invasion were evaluated. Western blot analysis was used to assess the impact of AhR on the expression of apoptosis genes and epithelial-to-mesenchymal transition (EMT)-related genes. We established a mouse xenograft model to evaluate the effects of AhR on cervical cancer tumorigenesis. AhR expression was downregulated in both patient tissues and cell lines. AhR overexpression reduced cell viability, colony formation, and migration/invasion, induced cell cycle arrest and apoptosis in cervical cancer cells, and suppressed tumor growth and weight in the xenograft model. Immunohistochemical analysis confirmed reduced cell proliferation and increased apoptosis in the HeLa xenografts. AhR overexpression downregulated cell survival and EMT-promoting genes, and upregulated apoptosis-promoting and EMT-suppressing genes. AhR is a crucial tumor suppressor in cervical cancer, suggesting potential therapeutic implications for its upregulation in cervical cancer management.