Long non-coding RNA HOTAIR promotes cervical cancer progression through regulating BCL2 via targeting miR-143-3p

Cancer Biol Ther. 2018 May 4;19(5):391-399. doi: 10.1080/15384047.2018.1423921. Epub 2018 Feb 6.

Abstract

Background: HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) widely involved in the progression of numerous malignancies. Whereas, the potential molecular mechanism of HOTAIR involved in cervical cancer progression is still needed to be elaborated.

Methods: The expression of HOTAIR and miR-143-3p were detected in cervical cancer tissues and cells by qRT-PCR. MTT and flow cytometry analysis were performed to measure cell proliferation and apoptosis. Bioinformatics, Dual-Luciferase reporter and RIP were used to analyze the possible correlation between HOTAIR, miR-143-3p and BCL2. The expression of Bax and BCL2 was detected by western blot. Mice xenograft model was established to confirm the role of HOTAIR on tumor growth in vivo.

Results: HOTAIR expression was elevated while miR-143-3p expression was reduced in cervical cancer tissues and cell lines. HOTAIR knockdown suppressed proliferation and enhanced apoptosis in cervical cancer cells. Moreover, HOTAIR could function as a sponge for miR-143-3p. The inhibitory effect of HOTAIR knockdown on cervical cancer cells growth was abolished following decrease of miR-143-3p expression. Furthermore, HOTAIR promoted BCL2 expression by modulating miR-143-3p. BCL2 overexpression attenuated the tumor-suppressive effect of miR-143-3p in cervical cancer. Finally, the carcinogenicity of HOTAIR was validated in mice.

Conclusions: HOTAIR promoted cervical cancer cell growth by modulating BCL2 via miR-143-3p, hinting a novel regulatory mechanism and potential therapeutic target in cervical cancer.

Keywords: BCL2; HOTAIR; cervical cancer; lncRNA; miR-143-3p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • HeLa Cells
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • BCL2 protein, human
  • HOTAIR long untranslated RNA, human
  • MIRN143 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding