Upregulation of the miR-212/132 cluster suppresses proliferation of human lung cancer cells

Abstract

Abstract. Lung cancer is the leading cause of cancer-related mortality worldwide. microRNAs (miRNAs) are small posttranscriptional regulatory non-coding RNAs that function as oncogenes or tumor suppressors in human cancers. Emerging evidence reveals that deregulation of miRNAs contributes to the progression of human lung cancer, which is the leading cause of cancer-related deaths worldwide. In the present study, we found that upregulation of the miR-212/132 cluster significantly suppressed the growth and focus formation of A549 and H1299 cells. Moreover, forced expression of this cluster conferred radiosensitivity and inhibited the migration of lung cancer cells, whereas downregulation of miR-212/132 reversed the above effects. Furthermore, miR-212/132 overexpression induced cell cycle arrest at the G1/S phase transition of the lung cancer cells, and inhibition of miR-132 and miR-212 abrogated this arrest. In addition, miR-212/132 overexpression increased the percentage of cells undergoing apoptosis. Cells transfected with the miR-212/132 cluster exhibited upregulated p21 expression and reduced cyclin D1 expression. Conversely, cells transfected with the miR-212/132 inhibitor showed reduced expression of p21 and upregulated expression of cyclin D1, suggesting that miR-212/132 may mediate proliferation and cell cycle arrest through p21 and cyclin D1. Our study provides insight into the biological function of the miR-212/132 cluster in lung cancer. The present study may provide a potential therapeutic target for the treatment of lung cancer.

Hyperosmotic stimulus study discloses benefits in ATP supply and reveals miRNA/mRNA targets to improve recombinant protein production of CHO cells

“…Further the significant upregulation of CDK1A in osmotically stressed CHO cells together with G1‐phase arrest, increased q ATP and enhanced q p may elucidate CDK1A's q p enhancing role that had been described in previous cell cycle engineering studies . Overexpression of miR‐132, miR‐194 and miR‐215 may potentially enhance q p as this was shown to induce p53/CDK1A(p21) mediated cell cycle arrest in G1‐phase . The hypothesized regulatory connection between miR‐183, EGR 1 and cell cycle arrest together with the q p enhancing effect described by Strotbek et al (2013) give point to miR‐183 as the most promising candidate for subsequent cell line engineering studies .…”

“…An either oncogenic or tumor suppressive role in cancer cells was reported for miR‐132, miR‐183 and miR‐182 . Overexpression of miR‐132, miR‐194 and miR‐215 resulted in a p53/CDK1A mediated cell cycle arrest in G1‐phase . Increased product titers and enhanced q p in combination with a decrease in cell growth was reported for recombinant CHO cell lines which had transiently been transfected with human miR‐183 .…”

MicroRNA-320 regulates the radiosensitivity of cervical cancer cells C33AR by targeting β-catenin

“…The expression of miRNA-320 in C33AR cells was significantly lower than that in C33A cells. Several differentially expressed miRNAs in this profile were previously reported to have a role in tumorigenesis, including the development of radioresistance (17,18). These results indicated that differentially expressed miRNAs may contribute to the acquisition of radioresistance in cervical cancer.…”

The microRNA-212/132 cluster regulates B cell development by targeting Sox4

“…In fact, it has been demonstrated that miR-212/132 is deregulated in cancers of various forms, including B cell leukemias, and that up-regulation of miR-212/132 in lung cancers inhibits proliferation and progression of the disease (Pede et al, 2013;Zhang et al, 2014;Jiang et al, 2015;Tavolaro et al, 2015). We found that enforced expression of miR-132 in donor cells from E-myc mice, which are prone to develop pre-B and immature B cell lymphomas and leukemias, had a strong protective effect on cancer development.…”