MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1

Abstract

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence, it is imperative to determine reliable biomarkers of lung cancer prognosis. MicroRNA-490-3p has been previously reported to be a positive prognostic biomarker for hepatocellular cancer. However, its role in human lung cancer has not yet been elucidated. Here, we report that hsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies of hsa-miR-490-3p showed that it regulates cell proliferation and is required for induction of in vitro migration and invasion-the latter being a hallmark of epithelial to mesenchymal transition. In situ analysis revealed that hsa-miR-490-3p targets poly r(C)-binding protein 1 (PCBP1), which has been previously shown to be a negative regulator of lung cancer metastasis. Reporter assays confirmed PCBP1 as a bona fide target of miR-490-3p, and metagenomic analysis revealed an inverse relation between expression of miR-490-3p and PCBP1 in metastatic lung cancer patients. In fact, PCBP1 expression, as detected by immunohistochemistry, was undetectable in advanced stages of lung cancer patients' brain and lymph node tissues. Xenograft tail vein colonization assays proved that high expression of miR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest that hsa-miR-490-3p might be a potential biomarker for lung cancer prognosis. In addition, we can also conclude that the lung cancer cells have evolved refractory mechanisms to downregulate the expression of the metastatic inhibitor, PCBP1.

microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2

“…Lung cancer is the most common cause of cancer-related mortality both for men and women worldwide, with an estimated of 1.4 million deaths per year (1,2). There are two principal forms of lung cancer: Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) (3).…”

MiR‐490‐5p inhibits the metastasis of hepatocellular carcinoma by down‐regulating E2F2 and ECT2

“…Besides, miRNAs play roles in various cellular processes, including cell proliferation, differentiation, development, and apoptosis . Recently, it has been reported that cancer tissues are a vital source of miRNAs, and miRNAs can function as tumor oncogenes or suppressors . Current researches suggest that miRNA provides a novel molecular approach to understand HCC pathogenesis.…”

“…As a kind of endogenous, small non-coding RNAs, microRNAs (miRNAs) can regulate gene expression by repressing translation or promoting mRNA degradation. 6 Besides, miRNAs play roles in various cellular processes, including cell proliferation, differentiation, development, and apoptosis. 7 Recently, it has been reported that cancer tissues are a vital source of miRNAs, and miRNAs can function as tumor oncogenes or suppressors.…”

Polycomb complex mediated epigenetic reprogramming alters TGF‐β signaling via a novel EZH2/miR‐490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas

“…Interestingly, miR‐490‐3p also becomes important as it has been shown to be downregulated in multiple tumors including gastric cancer, ovarian, osteosarcoma, breast, colorectal and endometrial cancer where it has been shown to play a tumor suppressive role . In contrast, its upregulated expression has also been reported in lung and hepatocellular carcinoma where it functioned as an oncomiR . We also report for the first time that miR‐490‐3p in GBM induces tumor suppression via inhibiting cell proliferation, anchorage independence, migration, EMT and spheroid‐forming ability and by inducing apoptosis in GBM cells.…”

“…[19][20][21][22][23][24][25][26][27][28][29][30][31] In contrast, its upregulated expression has also been reported in lung and hepatocellular carcinoma where it functioned as an oncomiR. 32,33 We also report for the first time that miR-490-3p in GBM induces tumor suppression via inhibiting cell proliferation, anchorage independence, migration, EMT and spheroid-forming ability and by inducing apoptosis in GBM cells. Also, previously reported EZH2 mediated promotion of GBM cell migration 3 and downregulation of miR-490-3p (as per our study) indicates EZH2 role in promoting GBM cell migration at least in part via the suppression of miR-490-3p.…”