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MicroRNA-218 enhances gastric cancer cell cisplatin sensitivity by targeting survivin
Zhandong Zhang1, Ye Kong1, Wei Yang1
1Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
Abstract:
Gastric cancer (GC) is one of the most prevalent types of cancer worldwide. Cisplatin based chemotherapy is the primary strategy implemented for the treatment of G; however, chemoresistance is a major problem. Previous studies have indicated that microRNAs (miRs) are associated with chemoresistance in various types of cancer and that miR-218 specifically, serves important roles in the growth of GC cells. The present study assessed the potential biological roles of miR-218 in GC cell cisplatin (DDP) resistance. The results obtained from a polymerase chain reaction assay indicated that the expression of miR-218 was decreased in cisplatin resistant SGC7901/DDP cells compared with SGC7901 cells. Furthermore, MTT results indicated that the upregulation of miR-218 expression significantly enhanced SGC7901/DDP cell sensitivity to DDP. The results of a dual-luciferase assay indicated that survivin was a direct target gene of miR-218. Results also demonstrated that miR-218 was overexpressed in SGC7901/DDP cells and that the downregulation of survivin expression enhanced SGC7901/DDP cell sensitivity to DDP. Further study demonstrated that the upregulation of miR-218 decreased the expression of survivin in SGC7901/DDP cells and induced apoptosis. The findings of the present study indicated that the induction of miR-218 enhanced GC cell DDP resistance via the regulation of survivin, which may potentially benefit the clinical treatment of GC in the future.
Insights
MicroRNA-218 (miR-218) levels are decreased in gastric cancer cells resistant to cisplatin chemotherapy. Upregulating miR-218 enhances sensitivity to cisplatin by targeting survivin, offering potential new treatments for gastric cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality globally.
- Cisplatin-based chemotherapy is a primary treatment for GC, but chemoresistance remains a significant challenge.
- MicroRNAs (miRs) are implicated in cancer chemoresistance, with miR-218 showing roles in GC cell growth.
Purpose of the Study:
- To investigate the biological role of miR-218 in cisplatin (DDP) resistance in gastric cancer cells.
- To determine the relationship between miR-218 expression, survivin, and DDP sensitivity in GC.
Main Methods:
- Polymerase chain reaction (PCR) to assess miR-218 expression levels.
- MTT assay to evaluate cell viability and sensitivity to DDP.
- Dual-luciferase reporter assay to identify direct target genes of miR-218.
Main Results:
- miR-218 expression was significantly decreased in DDP-resistant GC cells (SGC7901/DDP) compared to sensitive cells.
- Upregulation of miR-218 increased DDP sensitivity in SGC7901/DDP cells.
- Survivin was identified as a direct target gene of miR-218; miR-218 overexpression reduced survivin levels, induced apoptosis, and enhanced DDP sensitivity.
Conclusions:
- miR-218 enhances DDP sensitivity in gastric cancer cells by downregulating survivin.
- Modulating miR-218 may represent a promising therapeutic strategy to overcome chemoresistance in GC treatment.
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