J Cancer 2021; 12(18):5394-5403. doi:10.7150/jca.59747 This issue

Research Paper

MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling

Yingying Huang1,2, Xiaoxiao Du1, Xiangliu Chen1, Chuanzhi Chen1, Haiyong Wang1, Yan Yang1, Lisong Teng1✉

1. Department of oncological surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University.
2. Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, China.

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Huang Y, Du X, Chen X, Chen C, Wang H, Yang Y, Teng L. MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling. J Cancer 2021; 12(18):5394-5403. doi:10.7150/jca.59747. Available from https://www.jcancer.org/v12p5394.htm

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Graphic abstract

Objective: Gastric cancer (GC) is a type of highly malignant cancer. Although the diagnostic and therapeutic methods are innovating, the outcome of GC patients is still poor. Therefore, our research was carried out to explore potential molecular mechanism in the diagnosis of GC.

Materials and methods: Bioinformatics analyses were used to obtain microRNA and target mRNA of interest. The expression level of miR-301a-5p and Scinderin (SCIN) mRNA were detected by quantitative real-time PCR (qRT-PCR). Western blot assay was used to investigate SCIN protein level. Cell Counting Kit-8 assay (CCK-8) and colony formation assay were used to investigate cell proliferation ability. Transwell assay was employed to examine cell motility. The interaction between miR-301a-5p and SCIN mRNA was verified by dual-luciferase reporter assay.

Results: The qRT-PCR analysis revealed that the expression of miR-301a-5p was higher in gastric cancer tissues than para-cancer tissues (P<0.05). Cox regression analysis showed upregulated miR-301a-5p was associated with larger tumor size (P=0.036) and more advanced TNM stage (P=0.048). The Kaplan-Meier analysis showed a correlation between increased miR-301a-5p expression and shorter overall survival (OS)(P=0.018). By using bioinformatic analysis, SCIN was predicted as one of the targets of miR-301a-5p. Overexpressing miR-301a-5p promoted proliferation and motility of GC cells while knockdown of SCIN exhibited the same performance. Further, we verified the alteration of miR-301a-5p and SCIN expression level could affect the epithelial-mesenchymal transition (EMT) progression on GC cells via STAT3 and NF-κB signaling.

Conclusion: Highly expressed miR-301a-5p was associated with aggressiveness of GC. Upregulation of miR-301a-5p promoted malignant phenotype of GC by targeting SCIN. The present results indicated miR-301a-5p might be a promising molecule in the prognosis of GC.

Keywords: MicroRNA, miR-301a-5p, gastric cancer (GC), progression, EMT