LncRNA FGD5-AS1 potentiates autophagy-associated doxorubicin resistance by regulating the miR-154-5p/WNT5A axis in osteosarcoma

Cell Biol Int. 2022 Nov;46(11):1937-1946. doi: 10.1002/cbin.11889. Epub 2022 Aug 30.

Abstract

Osteosarcoma is prevalent in children and adolescent. The oncogenic function of long-chain noncoding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) has been reported. However, the function of FGD5-AS1 in doxorubicin-resistance in osteosarcoma remains to be illucidated. Quantitative real-time PCR (qRT-PCR) and western blot analysis (WB) were used to measure the expression of FGD5-AS1, miR-154-5p, WNT5A and autophagy proteins. MTT assay was used to assess cell viability and transwell assay was performed to evaluate migration. A nude mouse xenograft model was developed to verify the function of FGD5-AS1 in vivo. FGD5-AS1 was upregulated in doxorubicin-resistant (DXR) osteosarcoma cells. Knockdown of FGD5-AS1 suppressed osteosarcoma cell proliferation, migration, and autophagy. FGD5-AS1 upregulated WNT5A expression via sponging miR-154-5p. Furthermore, FGD5-AS1 enhanced osteosarcoma cell chemotherapy resistance through upregulation of WNT5A by inhibiting miR-154-5p. Suppression of FGD5-AS1 significantly suppressed tumor growth in nude mice. FGD5-AS1 may promote chemoresistance through WNT5A-induced autophagy by sponging miR-154-5p in osteosarcoma cells.

Keywords: FGD5-AS1; WNT5A; miR-154-5p; osteosarcoma.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteosarcoma* / drug therapy
  • Osteosarcoma* / genetics
  • Osteosarcoma* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Wnt-5a Protein / genetics
  • Wnt-5a Protein / metabolism

Substances

  • FGD5 protein, human
  • Guanine Nucleotide Exchange Factors
  • MIRN154 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • WNT5A protein, human
  • Wnt-5a Protein
  • Doxorubicin