Long Non-coding RNA LOXL1-AS1 Facilitates Colorectal Cancer Progression via Regulating miR-1224-5p/miR-761/HK2 Axis

Biochem Genet. 2022 Dec;60(6):2416-2433. doi: 10.1007/s10528-022-10226-3. Epub 2022 Apr 20.

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Long non-coding RNAs (lncRNAs) play crucial roles in the development of malignant tumors. The present study aimed to explore the function and potential mechanism of lncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) in CRC. The abundance of LOXL1-AS1, miR-1224-5p, miR-761, and hexokinase 2 (HK2) was detected by quantitative real-time PCR or western blot assay. Cell proliferation was assessed by Cell Counting Kit-8 and colony formation assays. Cell apoptosis, invasion, and migration were examined by flow cytometry, transwell assay, and wound healing assay. Glycolysis was evaluated by detecting glucose consumption, lactate production, and ATP/ADP ratios. Xenograft assay was used for in vivo tumor growth analysis. LOXL1-AS1 and HK2 levels were increased, while miR-1224-5p and miR-761 levels were reduced in CRC tissues and cells. Knockdown of LOXL1-AS1 suppressed CRC cell proliferation, invasion, migration, and glycolysis, and induced cell apoptosis. Silencing of LOXL1-AS1 blocked tumor growth in vivo. Moreover, LOXL1-AS1 accelerated CRC cell progression by absorbing miR-1224-5p/miR-761. Besides, miR-1224-5p and miR-761 inhibited CRC cell progression via targeting HK2. LOXL1-AS1 contributed to CRC progression via modulating miR-1224-5p/miR-761/HK2 pathway.

Keywords: Colorectal cancer; HK2; LOXL1-AS1; miR-1224-5p; miR-761.

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Amino Acid Oxidoreductases / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Gene Expression Regulation, Neoplastic
  • Hexokinase / genetics
  • Hexokinase / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Hexokinase
  • LOXL1 protein, human
  • Amino Acid Oxidoreductases
  • MIRN1224 microRNA, human
  • microRNA761 microRNA, human