BMC Cancer最新文献

Background: ITGA5 is an oncogene that performs its biological function by integrating the intracellular structure and extracellular matrix. We found that ITGA5 is highly expressed in gastric tumors and is closely related to proliferation and metastasis. Multiple miRNAs regulate the ITGA5 gene during the occurrence and development of tumors. This study aimed to explore the role of targeting miRNAs upstream of ITGA5 in the regulation of the proliferation, invasion, and migration of gastric cancer cells.

Methods: Target miRNA molecules regulating the ITGA5 gene were predicted using four bioinformatics databases (TargetScan、miRDB、miRTarBase and mirDIP). The unreported miRNAs with high correlation were selected, and their expression in gastric cancer was assessed using qRT-PCR and western blot. The miRNAs with potential targeting abilities were further verified by dual luciferase reporter gene experiment. The effects of miR-330-5p and ITGA5 on the proliferation, invasion, and migration of gastric cancer cells were evaluated using CCK8, clonogenic assay, and Transwell chamber assay, respectively.

Results: Six miRNAs (miR-26a-5p、miR-92a-3p、miR-148a-3p、miR-148b-3p、miR-330-5p and miR-152-3p) were identified. miR-330-5p was found to target and regulate ITGA5. In vitro experiments demonstrated that miR-330-5p mimic significantly inhibited the proliferation, invasion, and migration of gastric cancer cells compared with the control group (p < 0.05). Transfection of miR-330-5p mimic into gastric cancer cells overexpressing ITGA5 (OE-ITGA5) significantly prevented the ability of OE-ITGA5 to promote the proliferation, invasion, and migration of gastric cancer cells (P < 0.05). In addition, miR-330-5p mimic reduced ITGA5 expression in gastric cancer cells and partially prevented FAK/AKT signaling pathway activated by the ITGA5 gene. An miR-330-5p inhibitor increased ITGA5 expression in gastric cancer cells, and partially prevented blockage of the FAK/AKT signaling pathway by sh-ITGA5.

Conclusions: miR-330-5p was shown to affect the proliferation, invasion, and migration of gastric cancer cells by mediating ITGA5 through a mechanism possibly associated with the regulation of the FAK/AKT signaling pathway.

Background: Enhancer RNAs (eRNAs) have emerged as important regulators of gene expression and may reshape the therapeutic landscape of prostate cancer. However, their global landscape and clinical relevance in prostate cancer remain unclear.

Methods: We systematically integrated prostate cancer multi-omics and functional genomics datasets to characterize genome-wide eRNA transcription, construct eRNA-centered regulatory networks, and link eRNA-regulated genes to clinical outcomes. Representative eRNAs and their predicted target genes were further subjected to siRNA-mediated knockdown and functional validation in prostate cancer cell lines.

Results: We identified 13,595 eRNAs and 1,573 eRNA-regulated genes, including 266 transcription factors and 85 RNA-binding proteins. eRNA-regulated genes showed higher expression levels, lower variability, and enrichment in prostate cancer-related pathways. A five-gene eRNA-associated signature stratified patients into high- and low-risk groups with AUCs of 0.85, 0.77, and 0.89 for 1-, 3-, and 5-year survival and remained an independent prognostic factor. The two risk groups exhibited distinct genetic, transcriptomic, and epigenetic features. Functional validation further demonstrated that knockdown of representative eRNAs suppressed prostate cancer cell proliferation, migration, and invasion, accompanied by reduced expression of the target genes NUP93 and BICD1.

Conclusion: These findings indicate that eRNAs may contribute to prostate cancer biology and could serve as useful markers for prognosis and pathway characterization.