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. 2021 Aug;66(8):2651-2660.
doi: 10.1007/s10620-020-06579-7. Epub 2020 Sep 10.

MiR-325 Promotes Oxaliplatin-Induced Cytotoxicity Against Colorectal Cancer Through the HSPA12B/PI3K/AKT/Bcl-2 Pathway

Li Zhang  1 , Heping Chen  1 , Yueqiong Song  1 , Qing Gu  1 , Lu Zhang  1 , Qin Xie  1 , Jin Xu  1 , Min Zhang  2
Affiliations

MiR-325 Promotes Oxaliplatin-Induced Cytotoxicity Against Colorectal Cancer Through the HSPA12B/PI3K/AKT/Bcl-2 Pathway

Li Zhang et al. Dig Dis Sci. 2021 Aug.

Abstract

Background: Oxaliplatin is one of the most effective chemotherapeutic drugs used for the treatment of colorectal cancer (CRC). However, intervention that attenuates the resistance of oxaliplatin is still required in the treatment of CRC.

Aims: To investigate the role of miR-325 in changing the oxaliplatin sensitivity to CRC cells.

Methods: Expression of miR-325 in colorectal cancer tissues and cell lines was measured by using qRT-PCR analysis. Cytotoxicity of oxaliplatin to control or miR-325-overexpressed HT29 and SW480 cells was evaluated by CCK-8 assays. Luciferase reporter assay was used to confirm the regulation of miR-325 on HSPA12B. Flow cytometry was performed to detect the mitochondrial membrane potential and cell apoptosis.

Results: Expression of miR-325 was decreased in colorectal cancer tissues and cell lines. However, overexpression of miR-325 can decrease the 50% inhibiting concentration of oxaliplatin to colorectal cancer cell lines HT29 and SW480. Mechanically, we confirmed that miR-325 targeted HSPA12B in colorectal cancer. Therefore, overexpression of miR-325 inhibited the phosphorylation of PI3K and AKT and decreased the expression of Bcl-2 to promote the oxaliplatin-induced mitochondrial apoptosis in colorectal cancer.

Conclusions: MiR-325 sensitizes the colorectal cancer cells to oxaliplatin-induced cytotoxicity through the HSPA12B/PI3K/AKT/Bcl-2 pathway.

Keywords: Bcl-2; Colorectal cancer; HSPA12B; Oxaliplatin; PI3K/AKT; miR-325.

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