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Tumor Biology

, Volume 37, Issue 11, pp 15221–15228 | Cite as

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

  • Jindong Li
  • Qingchuan Feng
  • Xudong Wei
  • Yongkui Yu
Original Article

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.

Keywords

Poly r(C)-binding protein 1 PCBP1 miR-490-3p Lung cancer EMT Metastasis 

Notes

Compliance with ethical standards

The study protocol was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University, China. Experiments were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University and were performed in accordance to the “Guidelines for the Welfare of Animals in Experimental Neoplasia” published by The United Kingdom Coordinating Committee on Cancer Research.

Conflicts of interest

None.

Supplementary material

13277_2016_5347_MOESM1_ESM.xlsx (17 kb)
ESM 1 (XLSX 16 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jindong Li
    • 1
  • Qingchuan Feng
    • 2
  • Xudong Wei
    • 3
  • Yongkui Yu
    • 1
  1. 1.Department of Thoracic SurgeryThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Department of Cell Biology and Medical GeneticsBasical Medical CollegeZhengzhouChina
  3. 3.Department of Thoracic SurgeryAnyang Cancer HospitalAnyangChina

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