LncRNA HOXC-AS3 overexpression inhibits TGF-β2-induced colorectal cancer cell migration and invasion by sponging miR-1269

Hum Exp Toxicol. 2022 Jan-Dec:41:9603271221093630. doi: 10.1177/09603271221093630.

Abstract

Objective: Long non-coding RNA (lncRNA) HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown.

Methods: The expression of HOXC-AS3 and TGF-β2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-β2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-β2 in regulating CRC cell invasion and migration.

Results: HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-β2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-β2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-β2, while the expression of HOXC-AS3 was not affected by TGF-β2. Transwell migration and invasion assay showed that overexpression of TGF-β2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-β2. MiR-1269 increased the expression of TGF-β2. HOXC-AS3 directly interacted with miR-1269 in CRC cells.

Conclusions: Upregulation of HOXC-AS3 inhibited TGF-β2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.

Keywords: TGF-β2; colorectal cancer; lncRNA HOXC-AS3; prognosis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transforming Growth Factor beta2 / genetics
  • Transforming Growth Factor beta2 / metabolism

Substances

  • MIRN1269 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transforming Growth Factor beta2