Salidroside Inhibits the Proliferation of Gastric Cancer Cells by Regulating the miR-1343-3p/SOX18 Signaling Axis

ZHANG Zhendong, CAO Xiaolan, HOU Xinrui, CAO Mingyuan, DU Yuxin, ZHANG Jie, SUN Yanan, WANG Xiaoping

Abstract


Objective 

 To investigate the molecular mechanism by which salidroside inhibits the proliferation of gastric cancer (GC) cells through upregulation of miR-1343-3p.

Methods 

 RNA databases were used to screen for mRNAs associated with tumor proliferation and with miR-1343-3p, and exhibiting significant changes in their expression levels after salidroside treatment of human GC cells. Gene matching and immunoprecipitation of RNA-binding proteins were conducted to analyze the association between miR-1343-3p and SOX18. Immunocytochemistry was performed to determine the localization of SOX18 protein. The effect of salidroside on the proliferation of human GC cells (MGC-803 and AGS) was determined by CCK-8 assay. Human GC cells were divided into a blank control group and low- and high-dose salidroside groups. The expression of miR-1343-3p and SOX18 mRNA was measured by real-time quantitative fluorescence PCR (qPCR). The protein expression of SOX18 was measured by Western blot. GC cells were co-transfected with miR-1343-3p mimic and miR-1343-3p inhibitor, respectively, via LipofectamineTM 2000 liposomes. The expression of miR-1343-3p and SOX18 mRNA was measured by qPCR, and the protein expression of SOX18 was measured by Western blot.

Results 

 Through bioinformatic analysis, SOX18 was identified as a downstream target of miR-1343-3p. Gene alignment confirmed the presence of specific binding sites between the two genes, and immunoprecipitation of RNA-binding proteins validated the targeting relationship between them (P < 0.05). Immunocytochemistry demonstrated the nuclear localization of SOX18 protein. CCK-8 assay findings demonstrated that salidroside significantly inhibited the proliferation of GC cells in a time- and dose-dependent manner. Compared with the blank control group, salidroside-treated GC cells showed decreased expression of both SOX18 mRNA and protein (P < 0.05) and an increased miR-1343-3p expression (P < 0.05). Compared with the control group, GC cells in the miR-1343-3p mimic group exhibited increased expression of miR-1343-3p and decreased expression of SOX18 mRNA and protein. In contrast, GC cells in the miR-1343-3p inhibitor group showed decreased expression of miR-1343-3p and increased expression of SOX18 mRNA and protein (all P < 0.05).

Conclusion 

 Salidroside may inhibit the proliferation of GC cells by regulating the miR-1343-3p/SOX18 signaling axis and these regulators may present new potential therapeutic targets or biomarkers for gastric cancer.

 

Keywords: Gastric cancer, Salidroside, miR-1343-3p, SOX18

 

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