MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer

Abstract

Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial-mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

“…Previous studies have demonstrated that miR-30a is involved in the progression of various malignant tumors (20,21,23). However, the mechanism of miR-30a in the progression of cervical cancer remains unclear.…”

“…Accumulating evidence indicates that the dysregulation of miR-30a contributes to various malignant tumors, including lung, thyroid, gastric, breast and colon cancer (18)(19)(20)(21)(22)(23). miR-30a promotes tumorigenesis in these cancers by directly targeting tumor-associated proteins.…”

MicroRNA-30a regulates zebrafish myogenesis via targeting the transcription factor Six1

“…Interestingly, the expression of miR30a decreases with the progression of lymphoma, leukemia, lung, ovarian, breast and colon cancer (Cheng et al, 2012;González-Gugel et al, 2013;Guan et al, 2012;Lee et al, 2012;Liu et al, 2013;Ma et al, 2012;Võsa et al, 2013), all cancers in which SIX1 overexpression has been detected (Behbakht et al, 2007;Ford et al, 1998;Mimae et al, 2012;Ono et al, 2012;Wang et al, 2011). Importantly, increased SIX1 expression enhances progression of RMS and several additional tumor types by re-activating many of the same signaling networks that SIX1 turns on developmentally to promote cell survival, proliferation and migration (Christensen et al, 2008;Khan et al, 1999;Yu et al, 2006;Yu et al, 2004).…”

“…In breast cancer and colon cancer, SIX1 induces an EMT and thereby promotes progression of these malignancies (McCoy et al, 2009;Micalizzi et al, 2009;Ono et al, 2012). Of note, miR30a has been implicated as a tumor suppressor in a variety of cancers, primarily through downregulation of EMT-driving proteins (Cheng et al, 2012;Kumarswamy et al, 2012). Given our demonstration that miR30a downregulates Six1 developmentally, and existing data that the two molecules have a reciprocal expression pattern in numerous of the same tumor types, it is tempting to speculate that miR30a loss might contribute to high Six1 expression in multiple types of cancer.…”

microRNA-10b promotes the migration of mouse bone marrow-derived mesenchymal stem cells and downregulates the expression of E-cadherin

“…At present, >1000 miRs have been identified in the human and mouse genomes, a number of which have been found to be involved in cell migration (4,5). It has been reported that miRs, including miR-let-7a, -16, -30a, -34a, -107, -125b, -200c, -203, -218, -424 and -488, inhibit the migration of specific tumor cells and other normal cell lineages (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, other miRs, including miR-10b, -20, -21 and -144, have been reported to promote cell migration (15)(16)(17)(18).…”