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Original Article

MicroRNA-221-3p promotes cell proliferation, migration, and invasion in gastric cancer by modulating PIK3R1

Mohanad Hasan, Reza Safaralizadeh, Mohammad Khalaj-Kondori, Saeid Latifi-Navid.


Background: Gastric cancer (GC), which is the fourth most prevalent cancer in the world is significantly threatened the health of people, particularly those in developing nations. Nearly all significant pathological and physiological mechanisms, including apoptosis, proliferation, cell cycle, differentiation, as well as DNA damage, are regulated by miRNAs. This study looked at the miR-221-3p expression and to identified it's target genes in GC tissue specimens and cell lines, to comprehend the miR-221-3p influence in the development of GC.
Methods: GC tissues and matched marginal tissues were taken from 50 patients undergo gastric surgery. MiR-221-3p mimics, inhibitors and negative controls (NC) were transfected into MKN-45 cells, using Lipofectamine RNAiMAX reagent. The proliferation was assessed by the MTT assay. Cell migration and invasion was assessed by Transwell assay. By combining Western blotting and qRT-PCR, the impact of miR-221-3p in the PIK3R1 expression in gastric cancer cells was examined.
Results: Overexpression of miR-221-3p significantly enhanced the migration, invasion and proliferation of gastric cancer cells, conversely, transfection of miR-221-3p inhibitor led to opposite effect caused by overexpression of this miRNA on phenotypic characteristics of gastric cancer cell line. Additional investigation revealed that PIK3R1 was downregulated significantly by overexpression of miR-221-3p. Whereas, when the MKN-45 cells transfected with miR-221-3p inhibitor, PIK3R1 was noticeably overexpressed.
Conclusions: Our current data indicate that miR-221-3p possibly work as a tumor promoter in the development of gastric cancer by negatively regulating PIK3R1 expression, hence miR-221-3p/ PIK3R1 highlighted as promising therapeutic targets or prognostic and diagnostic biomarkers for GC patients.

Key words: Gastric cancer; MicroRNAs; miR-221-3p; PIK3R1; Proliferation

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