MiR-4295 Attenuates the Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs by Inhibiting BCL2L11

INTRODUCTION: miRNA is a small intranuclear noncoding RNA, approximately 22 nucleotides (nt), that is aberrantly expressed in tumor cells and tissues. They play important regulatory roles in cell proliferation and chemosensitivity. Our study focuses on the expression of miR-4295 and its role in gastric cancer. MATERIALS AND METHODS: Real-time quantitative RT-PCR was used to detect miR-4295 and mRNA expression. Western blots were used to detect protein expression levels. Luciferase reporter test was used to verify BCL2L11 as a potential target for miR-4295. The GEPIA database was used to analyze a prognostic indicator of gastric cancer patients. The CCK-8 kit was used to evaluate the effect of miR-4295 in combination with chemotherapeutic drugs on cell viability. RESULTS: The results of real-time quantitative reverse transcription polymerase chain reaction showed that the expression level of miR-4295 was significantly upregulated in the cisplatin-resistant gastric cancer cell line SGC-7901/DDP. This study found that the upregulation of miR-4295 expression could significantly inhibit the expression of BCL2L11, while upregulating the expression of Bcl-2, and reducing the sensitivity of gastric cancer cells to chemotherapeutic drugs; while downregulating the expression of miR-4295 would produce the opposite biological effect. Further analysis using the GEPIA database suggested that BCL2L11 might play a potential role in the prognosis assessment of gastric cancer patients, and its expression was significantly correlated with Bcl-2. Additionally, the luciferase reporter gene experiment further verified that BCL2L11 was a potential target gene of miR-4295. DISCUSSION: During the occurrence and development of gastric cancer, the abnormal high expression of miR-4295 is widespread. Studies have shown that the upregulation of miR-4295 expression can significantly enhance the proliferation ability of tumor cells and reduce the sensitivity of cells to chemotherapy drugs such as docetaxel or cisplatin by inhibiting the expression of BCL2L11, while downregulating the expression of miR-4295 can produce the opposite biological effect. The above research results suggest that the regulatory relationship between miR-4295 and BCL2L11 may provide a potential new intervention strategy for the treatment of gastric cancer. CONCLUSION: Our study suggests that miR-4295 has the potential to be a therapeutic target for gastric cancer by targeting BCL2L11 to function as an oncogenic miRNA in gastric cancer. However, there are still many issues that need to be addressed. More research is required to find the optimal strategy and schedule for down-regulating miR-4295, as well as to determine the most feasible method for delivering this system to tumor cells. In summary, down-regulating miR-4295 is a promising strategy for reversing chemotherapy resistance, but more research is needed to clarify the above issues.