miR‐214 activates TP53 but suppresses the expression of RELA, CTNNB1, and STAT3 in human cervical and colorectal cancer cells

Abstract

High Mobility Group AT-hook 1 (HMGA1) was identified as a target of miR-214 in human cervical and colorectal cancers (CaCx and CRC) in a previous study. While the expression of miR-214 remains suppressed, HMGA1 behaves as a potent oncogene and plays crucial roles in several aberrant signalling pathways by interacting with intermediates like RELA, CTNNB1, STAT3, and TP53 in CaCx and CRC. Hypothetically, miR-214 should be able to regulate the stabilization of some of these intermediates through the regulation of HMGA1. This was assessed by ectopically expressing miR-214 or complementarily, by inhibiting the expression of HMGA1. In promoter luciferase assays, miR-214 inhibited NF-κB and Wnt activities but elevated TP53 activity in cancer cells. Further, miR-214 suppressed the expression of HMGA1, RELA, CTNNB1, and STAT3 while elevating TP53 levels, similar to when small interfering RNA (siRNA) against HMGA1 was used, as revealed by Western blotting. It is suggested that poor expression of miR-214, commonly reported in CaCx and CRC tissues, may not only result in the sustained expression of HMGA1 but also that of RELA, CTNNB1, and STAT3, and a congruent suppression of TP53 during cancer initiation/progression. These several states are, however, reversed when miR-214 is reintroduced and could explain the tumour suppressive functions observed in earlier studies. Further studies are, however, required to reveal how microRNA-mediated regulation of HMGA1 expression may affect individual signalling pathways in CaCx and CRC. Current results reveal that miR-214 is not only able to regulate the expression of its direct target, HMGA1, but also that of a few signalling intermediates like TP53, RELA, CTNNB1, and STAT3, with which HMGA1 interacts. These intermediates play crucial roles in signalling pathways commonly deregulated in human CaCx and CRC. Hence, it is proposed that miR-214 might act as a tumour suppressor by regulating several aberrant signalling pathways through HMGA1. This knowledge has the potential to help design novel therapeutic strategies in CaCx and CRC.

miR‐22 and miR‐214 targeting BCL9L inhibit proliferation, metastasis, and epithelial‐mesenchymal transition by down‐regulating Wnt signaling in colon cancer

“…Ectopic overexpression of miR‐214 inhibits cell proliferation and migration of human colon cancer cells. These results are similar to other findings in colon cancer (19, 44, 45). The underlying mechanism of miR‐214 in the progression of colon cancer remains to be clarified.…”

“…miR‐214 prohibits cell growth by targeting MELK in hepatocellular carcinoma (18). miR‐214 functions as an antitumor gene and activates TP53 but inhibits the expression levels of RELA, CTNNB1 , and STAT3 in colorectal and cervical cancer cells (19). These controversial data demonstrate that the role of miR‐214 is different depending on its target genes in different cancer types.…”

Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1

“…Increasing researches have demonstrated that miRNAs exert vital roles in various biological process associated with cancer, including cell proliferation, apoptosis, metastasis and chemotherapy-resistant [18][19][20][21]. Substantive investigations reveal that the aberrant levels of miRNAs are strongly linked to the growth and metastasis of ovarian cancer.…”

MicroRNA-214 Prevents Pulmonary Angiogenesis and Alveolarization in Rat Models with Bronchopulmonary Dysplasia via PlGF-Dependent STAT3 Signaling Pathway

“…On the basis of a prior study, PlGF could increase the phosphorylation of STAT3 [12]. MiR-214 has been proven to downregulate the expression of STAT3 in human cervical and colorectal cancer cells [29].…”