MicroRNAs Provide Feedback Regulation of Epithelial‐Mesenchymal Transition Induced by Growth Factors

Abstract

As regulators in gene expression, microRNAs take part in most biological processes including cell differentiation, apoptosis, cell cycle, and epithelial-to-mesenchymal transition (EMT). In order to evaluate their roles in EMT process, microRNA expression profile changes induced by EGF or TGF-β treatment on nasopharyngeal carcinoma cell HK-1 were analyzed, and miR-21, miR-148a, miR-505, and miR-1207-5p were found to be upregulated in growth factors-induced EMT process. miR-21 is already known as an oncogenic miRNA to promote metastasis, however, the exact functions of other three miRNAs in EMT are unclear. To our surprise, we found that miR-148a, miR-505, and miR-1207-5p can suppress EMT and metastasis phenotypes in HK-1 cells both in vitro and in vivo, which may relate to their inhibition on EMT and Wnt signaling molecules. MiRNAs confer robustness to biological processes by posttranscriptional repression of key transcriptional programs that are related to previous developmental stages or to alternative cell fates. Our findings indicate that miRNA feedback circuit is tuned to respond to growth factors-induced EMT, and we suggested a new negative feedback loop which may be an important element of the EMT process and confer biological robustness.

The relationship between vasculogenic mimicry and epithelial‐mesenchymal transitions

“…MicroRNAs are capable to target cancer-related genes, result in their translational repression or degradation and consequently, act as oncogenes or tumour suppressors [69]. Several microRNAs have been identified to regulate EMT.…”

“…MiR-205 can also sustain the differentiation of epithelial cells in mammary gland. MiR-148a, miR-505 and miR-1207-5p, induced by growth factors, act as a negative feedback loop of EMT [69,76]. The three microRNAs can be served as EMT and metastasis inhibitors by repressing expression of EMT-related molecules including Snail, fibronectin and b-catenin.…”

“…[ [69][70][71][72][73][74] MiR-205 Act with miR-200 synergistically to suppress ZEB and suppress EMT, as well as sustain the differentiation of epithelial cells in mammary gland. [74,75] MiR-148a, miR-505 and miR-1207-5p…”

“…[ 69,76] Snail/miR-34 feedback loop Control the epithelial plasticity and stimulate EMT in tumour progression. [77,78] MiR-29b Suppress EMT and metastasis progress in prostate cancer.…”

“…[76,79] MiR-148a Negatively regulate Met/Snail signalling and prevent EMT and metastasis in hepatoma cells. [69,76,80] EMT: epithelial-mesenchymal transition; ZEB: zinc-finger E-box binding homeobox; TGF-b: transforming growth factor-b. …”