Long noncoding RNA SNHG15 enhances the development of colorectal carcinoma via functioning as a ceRNA through miR-141/SIRT1/Wnt/β-catenin axis

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2536-2544. doi: 10.1080/21691401.2019.1621328.

Abstract

Colon cancer, also known as colorectal carcinoma (CRC), remains to be one of the most mainsprings of cancer-produced deaths entire world. We planned to grab the role and possible biological cause of a long noncoding RNA, namely, small nucleolar RNA host gene 15 (SNHG15), in CRC. The mRNA level of SNHG15 in CRC tissues and cells was detected, followed by investigating the impacts of the depression of SNHG15 on CRC cell proliferation (viability and colony-forming), apoptosis, migration, and invasion. Moreover, the association between SNHG15 and miR-141 and the correlation between miR-141 and SIRT1 were also explored. Besides, the influences of dysregulated SNHG15 on the Wnt/β-catenin signal-related proteins were determined. SNHG15 was highly expressed in CRC tissues and cells. Depression of SNHG15 depressed proliferation, enhanced apoptosis, and repressed the migration and invasion of CRC cells. In addition, SNHG15 presented a downside tendency on regulating miR-141, and the miR-141 inhibitor dramatically changeover the impacts of SNHG15 depression on tumor growth and metastasis. Moreover, SIRT1 was verified as a functional target of miR-141 in CRC cells. Besides, the suppression of SNHG15 remarkably controlled activating the Wnt/β-catenin signals, which was reversed after inhibiting miR-141 at the same time. The investigated results in this research revealed that the increased expression of SNHG15 may enhance the process of CRC by acting as a ceRNA in regulating SIRT1 expression by sponging miR-141. Thus we propose that Wnt/β-catenin signals may be a downriver regulator in mediating the impacts of SNHG15 in CRC and SNHG15-miR-141-SIRT1 axis may pave a new sight in explaining the biological processes of CRC.

Keywords: Colorectal cancer; SIRT1; SNHG15; Wnt/β-catenin signal; competitive endogenous RNA; miR-141.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Sirtuin 1 / metabolism*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • MIRN141 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Wnt Proteins
  • beta Catenin
  • Sirtuin 1