MIR4435-2HG, miR-125b-5p, and Sema4D axis affects the aggressiveness of colorectal cancer cells

Folia Histochem Cytobiol. 2022;60(2):191-202. doi: 10.5603/FHC.a2022.0018. Epub 2022 Jun 22.

Abstract

Introduction: The purpose of this study is to elucidate the impact of long non-coding RNA (lncRNA) MIR4435-2HG/microRNA (miR)-125b-5p/ Semaphorins 4D (Sema4D) on colorectal cancer (CRC) cell propagation and migration.

Material and methods: Sema4D expression in 73 pairs of CRC tissues and matched adjacent normal tissues was measured by qRT-PCR and western blot and its association with pathological characteristics of CRC patients was analyzed by chi-square test. Also, the expression of MIR4435-2HG, miR-125b-5p and Sema4D in CRC cell lines was detected by qRT-PCR and Western blot. Knockdown or overexpression of MIR4435-2HG, miR-125b- 5p and Sema4D were separately performed in Caco-2 and LoVo cells, and the cell propagation, migration and invasiveness were detected by cell-counting kit 8, scratch, and transwell assays.

Results: LncRNA MIR4435-2HG and Sema4D were highly expressed, while miR-125b-5p expression was decreased in CRC tissues and cells. Knockdown of MIR4435-2HG/Sema4D or overexpression of miR-125b-5p inhibited CRC cell proliferation and aggressiveness; overexpression of MIR4435-2HG/Sema4D or knockdown of miR-125b-5p prompted the malignant behaviors of cancer cells. MIR4435-2HG and Sema4D competitively bound to miR-125b-5p.

Conclusions: LncRNA MIR4435-2HG targets miR-125b-5p to upregulate Sema4D expression, and thus regulates CRC cell propagation, migration and invasiveness.

Keywords: cell lines; colorectal cancer; humans; invasion; migration; proliferation; survival analysis.

MeSH terms

  • Antigens, CD
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Semaphorins* / genetics
  • Semaphorins* / metabolism

Substances

  • Antigens, CD
  • CD100 antigen
  • MicroRNAs
  • RNA, Long Noncoding
  • Semaphorins