miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation

Abstract

We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

“…Of the five significantly upregulated miRNAs identified in this study, miR‐181a‐5p, miR‐181c‐5p, miR‐223‐3p, and miR‐342‐3p have been described as oncomiRs in other cancer types (Mi et al ., ; Tao et al ., ; Walter et al ., ; Wei et al ., ). Of these, miR‐181a‐5p, miR‐181c‐5p, and miR‐223‐3p have previously been identified as upregulated in 4–18 OS samples (Jones et al ., ; Lulla et al ., ; Maire et al ., ; Won et al ., ).…”

MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4

“…27 Mi et al validated that miR-181a-5p facilitated the development of GC via RASSF6-modulated MAPK signaling pathway. 28 Recently, miR-122-5p has been identified as a potential novel biomarker.…”

Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer

“…MiRNAs downregulate gene expression by binding to the 3′-untranslated regions (3′-UTR) of specific target messenger RNAs (mRNAs), resulting in inhibition of translation or mRNA degradation [5]. MiRNAs regulate numerous cellular processes, such as cell proliferation, apoptosis, migration, invasion and differentiation [6, 7]. Furthermore, aberrant expression of miRNAs have been reported in many cancers [8–10].…”