Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-378a/FSCN1 regulatory axis inhibits tumor stemness and increases the cytotoxicity of chemotherapeutic drugs in colorectal cancer cells

Taizhe Zhang, Jie Du, Sandan Li, Chuanming Zheng, Zhenjie Wang, Fuchen Xie

Department of Emergency Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province 233000, China;

For correspondence:- Fuchen Xie Email: xfc0215_vv@126.com Tel:+865523086034

Accepted: 19 December 2022 Published: 30 January 2023

Citation: Zhang T, Du J, Li S, Zheng C, Wang Z, Xie F. MiR-378a/FSCN1 regulatory axis inhibits tumor stemness and increases the cytotoxicity of chemotherapeutic drugs in colorectal cancer cells. Trop J Pharm Res 2023; 22(1):37-44 doi: 10.4314/tjpr.v22i1.6

© 2023 The authors.
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Abstract

Purpose: To evaluate the effect of miR-378a/FSCN1 axis on tumor stemness and aerobic glycolysis in colorectal cancer cells (CRC).

Methods: Abnormal expressions of miR-378a and FSCN1 in CRC tissues were analyzed through TCGA database. Cell viability and apoptosis were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay and flow cytometry, respectively, while expression of miR-378a was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, Western blotting assay was used to assess protein expressions. The miR-378a target was evaluated using ENCORI and confirmed by luciferase assay. Aerobic glycolysis was evaluated by determining glucose uptake, lactate production and lactate dehydrogenase (LDH) activity.

Results: Downregulation of miR-378a and upregulation of FSCN1 were observed in both CRC tissues and cell lines (p < 0.05). Overexpression of miR-378a and repression of FSCN1 reduced cell viability and tumor sphere formation, and induced cell apoptosis. Protein expression of SOX2, KLF4, Bmi1 and Oct-4 were downregulated by either the overexpression of miR-378a or repression of FSCN1 (p < 0.01). Glucose uptake, lactate production and LDH activity were inhibited by either overexpression of miR-378a or repression of FSCN1, while cytotoxicity of Dox and 5-Fu was increased by upregulation of miR-378a or downregulation of FSCN1 (p < 0.05). The predictive results of ENCORI demonstrated that FSCN1 was the direct target of miR-378a, and this was confirmed by luciferase assay results (p < 0.005). All the effects of miR-378a in CRC were reversed by overexpression of FSCN1 (p < 0.05).

Conclusion: This study has shown that miR-378a suppresses tumor stemness and increases the cytotoxicity of chemotherapeutic drugs by directly targeting FSCN1, resulting in the prevention of CRC tumorigenesis. Thus, these findings suggest a new approach to the chemotherapeutic management of CRC.

Keywords: miR-378a, FSCN1, Tumor stemness, Aerobic glycolysis, Colorectal cancer cells