Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1

J Cell Mol Med. 2021 Oct;25(19):9319-9330. doi: 10.1111/jcmm.16868. Epub 2021 Sep 12.

Abstract

Long non-coding RNA DLX6 antisense RNA 1 (DLX6-AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6-AS1, microRNA (miR)-193b-3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6-AS1/miR-193b-3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6-AS1, miR-193b-3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6-AS1/miR-193b-3p-related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6-AS1 and HOXA1 were up-regulated, and miR-193b-3p was down-regulated in TC. Depleted DLX6-AS1 or restored miR-193b-3p disturbed cell growth and promoted autophagy. DLX6-AS1 targeted miR-193b-3p and positively regulated HOXA1. miR-193b-3p inhibition mitigated the impaired tumorigenesis induced by down-regulated DLX6-AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6-AS1 depletion hinders TC cell growth and promotes autophagy via up-regulating miR-193b-3p and down-regulating HOXA1.

Keywords: HOXA1; autophagy; long non-coding RNA DLX6-AS1; metastasis; microRNA-193b-3p; thyroid carcinoma.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Autophagy / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Heterografts
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • MIRN193 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors
  • homeobox A1 protein