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MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer
Maolan Li1,2, Wei Chen1, Hongchen Zhang1,2
1Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Background:
Gallbladder cancer (GBC) is a malignant tumor highly resistant to chemotherapy. MicroRNAs (miRNAs) are found extensively involved in modulation of carcinogenesis and chemoresistance. This study aimed to investigate cisplatin (DDP)-susceptibility regulated by expression of the miRNAs and underlying pathways in GBC.
Results:
The microRNA-31 (miR-31) was selected by microarray due to the biggest fold change between DDP-resistant and parental cells. Ectopic overexpression of miR-31 decreased cell proliferation, viability and invasion capacity, but promoted apoptosis in DDP-resistant cells and in xenograft tumor models. Cell apoptosis and DDP-chemosensitivity was remarkably increased by knockdown of Src proto-oncogene (Src) expression, which was subsequently reversed by rescue of Src expression in miR-31-expressing cells.
Methods:
The microarray was used to select the candidate miRNA in two DDP-resistant GBC cell lines. The effect of regulated expression of the miRNA on cell migration, invasion, proliferation and apoptosis was examined by wound healing, transwell assays, CCK-8 assays, colony formation and flow cytometry assays, respectively. Xenograft tumor models were used to validate the function of the downstream target.
Conclusion:
Our results demonstrated that miR-31reduced significantly in GBC cells rendering resistance to cisplatin, and upregulated expression of miR-31 augmented chemosensitivity, presenting a therapeutic potential to overcome drug resistance in GBC.
Insights
MicroRNA-31 (miR-31) is significantly reduced in gallbladder cancer (GBC) cells, contributing to cisplatin resistance. Upregulating miR-31 enhances chemosensitivity, offering a potential therapeutic strategy for GBC drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gallbladder cancer (GBC) exhibits high resistance to chemotherapy.
- MicroRNAs (miRNAs) play a crucial role in cancer development and chemoresistance.
- Understanding miRNA regulation is key to overcoming drug resistance in GBC.
Purpose of the Study:
- To investigate the role of specific microRNAs in regulating cisplatin (DDP) susceptibility in GBC.
- To identify the underlying molecular pathways involved in miRNA-mediated chemoresistance.
- To explore the therapeutic potential of targeting miRNAs to overcome DDP resistance in GBC.
Main Methods:
- Microarray analysis to identify differentially expressed miRNAs in DDP-resistant GBC cells.
- In vitro assays (wound healing, transwell, CCK-8, colony formation, flow cytometry) to assess cell behavior.
- Xenograft tumor models to validate the in vivo function of the target miRNA and its downstream pathways.
Main Results:
- MicroRNA-31 (miR-31) showed the most significant fold change in DDP-resistant GBC cells.
- Overexpression of miR-31 reduced GBC cell proliferation, viability, and invasion while promoting apoptosis.
- Knockdown of Src proto-oncogene (Src) expression increased apoptosis and DDP-chemosensitivity, effects reversed by Src rescue.
Conclusions:
- miR-31 expression is significantly reduced in cisplatin-resistant GBC cells.
- Upregulating miR-31 enhances chemosensitivity and overcomes DDP resistance in GBC.
- miR-31 presents a promising therapeutic target for improving GBC treatment outcomes.

