Reduced long non-coding RNA PTENP1 contributed to proliferation and invasion via miR-19b/MTUS1 axis in patients with cervical cancer

Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4132-4144. doi: 10.26355/eurrev_202004_20993.

Abstract

Objective: Many studies showed that long non-coding RNAs (lncRNAs) may serve as prospective markers for patients with malignant cancers, including cervical cancer (CC). In this study, we mainly investigate the functions of lncRNA PTENP1 in the progression of human CC.

Materials and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect expression levels of PTENP1, miR-19b and MTUS1 in CC tissues, the adjacent tissues and CC cell lines. The correlations between PTENP1 with miR-19b, miR-19b with MTUS1 and PTENP1 with MTUS1 were analyzed. Overall survival (OS) of patients was analyzed using Kaplan-Meier method. Proliferation capacity was measured by CCK-8 assay and the invasion ability in CC cell line was detected by transwell assay. Western blot (WB) assay was performed to measure protein levels of tissues and CC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between PTENP1 and miR-19b, miR-19b and MTUS1.

Results: We found that PTENP1 was reduced in CC tissues and CC cell lines, which predicted the poor diagnosis of CC patients. MiR-19b was increased in CC tissues, which was negatively correlated with PTENP1 in CC tissues. MTUS1 was reduced in CC tissues, which was negatively correlated with miR-19b and positively correlated within PTENP1 CC tissues. Furthermore, PTENP1 overexpression inhibited cell proliferation ability and invasion capacity in HeLa cells, as well as repressed expressions of Cyclin D1, N-cadherin, and Vimentin. Moreover, Luciferase gene reporter assays verified that miR-19b was a direct target miRNA of PTENP1, and MTUS1 was identified as a direct target of miR-19b. In addition, the inhibited cell proliferation and invasion abilities in HeLa cells with p-PTENP1 were eliminated following with miR-19b mimic transfection.

Conclusions: According to the results, this study showed that PTENP1 was reduced in CC patients and it was a prognostic factor for CC patients. Furthermore, we firstly uncovered that PTENP1 could inhibit cell proliferation and invasion via miR-19b/MTUS1 in CC patients, which uncovered the tumor-suppressive role of PTENP1 in CC and suggested that it might be a potential target for treating human CC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN19 microRNA, human
  • MTUS1 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins