MiR-148a-3p suppresses the progression of gastric cancer cells through targeting ATP6AP2

Abstract

Purpose: Gastric cancer (GC) is one of the most frequent tumors with high mortality rate, worldwide. A proper understanding of the mechanism underlying its progression is required for its diagnosis and development of novel treatment option. MicroRNAs are associated with the development and advancement of different types of cancer, including GC. The current research was aimed at investigating the molecular and biological function of miR-148a-3p in GC development.Methods: A human normal gastric epithelial cell line, GES-1 (control) as well as four GC cell lines (NUGC-4, SNU-520, STKM-2 and MKN-74) were employed for the study. MiR-148a-3p and ATP6AP2 expression levels in GC cell lines were examined by RT-qPCR technique. Transfection procedure was used to upregulate miR-148a-3p expression in the MKN-45 cell line. MTT assay was utilized to evaluate cell viability in GC cell lines. The molecular interaction between miR-148a-3p and ATP6AP2 was predicted using bioinformatics system and the prediction was then validated by luciferase reporter assay.Results: Expression levels of miR-148-3p was low, whilst that of ATP6AP2 was high in GC cell lines. MiR-148a-3p overexpression resulted in the reduction of cell viability in GC cell lines. More so, it was confirmed that miR-148-3p, as a post-transcriptional regulator inhibited ATP6AP2 expression by having a negative association with it in GC cells. More so, ATP6AP2 was found to be a direct target of miR-148a-3p.Conclusion: Our results revealed that miR-148a-3p plays a crucial function in GC development through targeting ATP6AP2. This finding could be explored in the discovery of new therapeutic approaches for GC treatment.
 Keywords: ATP6AP2, Cell viability, Gastric cancer, miR-148a-3p, Progression

miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells

“…In contrast, the miR-148a-3p–predicted and miR-148a-3p–upregulated mRNAs did not share any genes in common ( Figure 1 J). Among 23 miR-148a-3p candidate targets, 7 genes, that is, ADAM17, 50 ATP6AP2, 51 CDKN1B, 52 MYBL1, 53 RAB12, 54 SOS2, 55 , 56 and UHMK1 57 were previously verified. By using quantitative reverse transcription PCR, we further validated the reduction of 20 out of 23 putative targets on miR-148a-3p overexpression ( Figure 1 K).…”

“…Among 23 miR-148a-3p candidate targets, 7 genes i.e. ADAM17 [35], ATP6AP2 [36], CDKN1B [37], MYBL1 [38], RAB12 [39], SOS2 [40,41], UHMK1 [42] were previously verified. We further validated by qRT-PCR the reduction of 20 out of 23 putative targets upon miR-148a-3p overexpression (Figure 1K).…”