RUNX3 regulates vimentin expression via miR‐30a during epithelial–mesenchymal transition in gastric cancer cells

Abstract

Runt-related transcription factor 3 (RUNX3) is a putative tumour suppressor via regulating the expression of a series of target genes. Clinical studies demonstrated that loss of RUNX3 expression is associated with gastric cancer progression and poor prognosis, but the underlying mechanism is not entirely clear. Accumulating evidence shows that the epithelial–mesenchymal transition (EMT) plays an important role in cancer relapse and metastasis. Therefore, we addressed whether RUNX3 has a role in the EMT in gastric cancer. Knockdown of RUNX3 promoted cell invasion and increased the protein expression of the mesenchymal marker vimentin in human gastric cancer cells. Overexpression of RUNX3 suppressed cell invasion and decreased the protein expression of vimentin in the cells and inhibited gastric cancer cells colonization in nude mice. Furthermore, overexpression of RUNX3 increased the expression of microRNA-30a (miR-30a), and miR-30a directly targeted the 3′ untranslated region of vimentin and decreased its protein level. miR-30a inhibitor abrogated RUNX3-mediated inhibition of cell invasion and downregulation of vimentin. Thus, RUNX3 suppressed gastric cancer cell invasion and vimentin expression by activating miR-30a. In gastric cancer patients, levels of RUNX3 were positively correlated with miR-30a and negatively associated with the levels of vimentin. Collectively, our data suggest a novel molecular mechanism for the tumour suppressor activity of RUNX3. Effective therapy targeting the RUNX3 pathway may help control gastric cancer cell invasion and metastasis by inhibiting the EMT.

Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing

“…Previous studies demonstrated that miR-30 can promote autophagy by beclin 1, 17,18 suppress growth and metastasis by targeting metadherin or denticleless protein homolog (DTL), [19][20][21] inhibit epithelial-to-mesenchymal transition by targeting Snai1, 22 and inhibit migration and invasion by downregulating vimentin expression. 23,24 Only a few studies reported that miR-30a existed in exosomes, and the levels of miR-30a derived from exosomes in urine, serum or plasma, and saliva could be used as non-invasive biomarkers for screening and diagnosing a certain type of cancer. [25][26][27] Our results indicate that hundreds of particular miRNAs were upregulated in exosomes from cancer cells compared with that from normal cells.…”

Overexpression of miR-30a in lung adenocarcinoma A549 cell line inhibits migration and invasion via targeting <italic>EYA2</italic>

“…These genes include PIK3CD [3], VIM [10], SEPT7 [12], DLL4 [9], CD99 [8], LOX [7], DTL [4], IRS2 [5], FOXL2 [13], etc. In addition, the signaling pathways of miR-30a implicated in the pathogenesis of cancers have also been reported.…”

“…It is clear now that miRNAs perform their biological functions by guiding the RNA-induced silencing complex (RISC) toward 3′ UTR of target mRNAs [2]. miR-30a locates in human chromosome 6q13 and increasing evidence indicates that miR-30a can act as a tumor suppressor to inhibit the growth of various tumors including colorectal carcinoma [3][4][5], breast cancer [6], anaplastic thyroid cancer [7], Ewing's tumor [8], clear cell renal cell carcinoma [9], gastric cancer [10], and nasopharyngeal carcinoma [10,11]. In addition, miR-30a also shows the feature of an oncogene.…”

miR‑30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy

“…To date, >200 miRNAs have been found to be associated with gastric cancer development, progression, and therapeutic response, and numerous studies have indicated that miRNAs may play an important role in the MDR of various types of cancer, including gastric cancer (9)(10)(11). It has previously been reported that miR-30a is significantly downregulated in gastric cancer cells (12,13). However, there is a lack of research on whether miR-30a regulation can affect the chemosensitivity of resistant gastric cancer cells, and the underlying mechanisms regarding the potential effects of miR-30a on drug resistance and cell autophagy require further investigation.…”