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

AbstractLung 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 thathsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies ofhsa-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 thathsa-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 confirmedPCBP1 as a bona fide target ofmiR-490-3p, and metagenomic analysis revealed an inverse relation between expression ofmiR-490-3p andPCBP1 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 ofmiR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest thathsa-miR-490-3p might be ...
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research