Down-Regulated LncRNA-HOTAIR Suppressed Colorectal Cancer Cell Proliferation, Invasion, and Migration by Mediating p21

Dig Dis Sci. 2018 Sep;63(9):2320-2331. doi: 10.1007/s10620-018-5127-z. Epub 2018 May 28.

Abstract

Background and aim: HOX transcript antisense intergenic RNA (HOTAIR) is a relatively well-understood RNA, which plays a central role in the pathogenesis of various tumors. The aim of the present study was to investigate the effect by which HOTAIR acts to influence the biological processes of colorectal cancer (CRC) through p21.

Methods: Reverse transcription quantitative polymerase chain reaction and Western blot methods were employed to provide verification regarding the changes in HOTAIR, PCNA, Ki67, p21, cyclin E, and CDK2 among the CRC tissues and cells. The correlation between the clinicopathological characteristics of patients and expression of HOTAIR and p21 was subsequently evaluated, followed by an analysis into the effects of HOTAIR on the biological processes of M5 cells.

Results: HOTAIR was found to be expressed at high levels, while p21 was determined to be at a low level among both the CRC tissues and the CRC cell lines. The expressions of HOTAIR and p21 were determined to be related to lymph node metastasis, tumor node metastasis, Dukes staging, distant metastases, histological types, and the degree of differentiation. Cells transfected with HOTAIR siRNA displayed inhibited rates of proliferation, invasion, and migration, as well as decreased cyclin E and CDK2, while apoptosis and p21 were increased.

Conclusion: The principal findings demonstrated that down-regulation of HOTAIR elicits an inhibitory effect on proliferation, invasion, and migration, while promoting the apoptosis of CRC cells through the up-regulation of p21. We believe that HOTAIR could represent a novel target for the treatment of CRC.

Keywords: Colorectal cancer; HOX transcript antisense RNA; Invasion; Migration; Proliferation; p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Caco-2 Cells
  • Cell Differentiation
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Time Factors
  • Young Adult

Substances

  • CDKN1A protein, human
  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • HOTAIR long untranslated RNA, human
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • RNA, Long Noncoding
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2