LncRNA NOC2L-4.1 functions as a tumor oncogene in cervical cancer progression by regulating the miR-630/YAP1 pathway

J Cell Biochem. 2019 Oct;120(10):16913-16920. doi: 10.1002/jcb.28949. Epub 2019 May 17.

Abstract

Long noncoding RNA (lncRNA) is a new class of noncoding RNA playing an indispensable role in different diseases by regulating miRNA. Our previous studies have suggested that miR-630 was decreased in patients with cervical cancer. Recently, studies have shown that lncRNA NOC2L-4.1 was abnormally expressed in patients with cervical cancer and can target miR-630. Therefore, we wanted to identify the integrated relationship between lncRNA NOC2L-4.1 and miR-630 in the pathological processes regarding cervical cancer either in vitro or in vivo. Quantitative reverse transcription-polymerase chain reaction detection shows that compared with human normal cervical epithelial cell, the expression of lncRNA NOC2L-4.1 was significantly increased and the expression of miR-630 was decreased in cell lines of cervical cancer. Moreover, luciferase reporter assay showed that miR-630 was a target of lncRNA NOC2L-4.1. The in vitro study found that downregulation of lncRNA NOC2L-4.1 suppressed cervical cancer cell migration (transwell assays) and proliferation (cell counting kit-8 and cloning formation assays). miR-630 specific inhibitor treatment reversed the inhibitory effect of lncRNA NOC2L-4.1 on cell proliferation and migration. Further studies also found that yes-associated protein 1 (YAP1) was the target of miR-630. Overexpression YAP1 suppressed miR-630 overexpression induced cell proliferation and inhibition of migration. Tumors induced by implantation of lncRNA NOC2L-4.1-knockdown Hela cells in nude mice showed that lncRNA NOC2L-4.1 silencing decreased the growth of tumors in both volume and weight by regulation of miR-630/YAP1. Taken together, our study reveals the important role of lncRNA NOC2L-4.1/miR-630/YAP1 regulatory network in cervical cancer, which provides new insights concerning the pathogenesis of cervical cancer.

Keywords: cervical cancer; long noncoding RNA NOC2L-4.1; miR-630; oncogene; yes-associated protein 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Oncogenes / genetics
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN630 microRNA, human
  • MicroRNAs
  • NOC2L protein, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human