Long non-coding RNA MSC-AS1 confers imatinib resistance of gastrointestinal stromal tumor cells by activating FNDC1 and ANLN-mediated PI3K/AKT pathway

Hum Cell. 2025 Jan 3;38(2):38. doi: 10.1007/s13577-024-01167-7.

Abstract

Imatinib resistance is a major obstacle to the successful treatment of gastrointestinal stromal tumors (GIST). Long non-coding RNAs (LncRNAs) have been identified as important regulatory factors in chemotherapy resistance. This study aimed to identify key lncRNAs involved in imatinib resistance of GISTs. First, MSC-AS1 was found to be upregulated in imatinib-resistant GIST tissues and imatinib-resistant GIST cells. Cellular experiments demonstrated that MSC-AS1 overexpression decreased imatinib sensitivity of GIST cells, evidenced by increased cell survival, colony formation, migration, and invasion. Moreover, suppression of MSC-AS1 improved the imatinib resistance of imatinib-resistant GIST cells. Furthermore, MSC-AS1 upregulated the expression of FNDC1 and Anillin via sponging miR-200b-3p, activated the phosphatidylinositol-3-kinase-AKT signaling pathway, and thereby driving imatinib resistance in vitro and in vivo. Overall, this study elucidates the crucial role and mechanism of MSC-AS1 in the imatinib resistance of GIST, providing the potential therapeutic strategy for overcoming the imatinib resistance of GIST.

Keywords: Gastrointestinal stromal tumors; Imatinib resistance; Long noncoding RNA.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm* / genetics
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors* / drug therapy
  • Gastrointestinal Stromal Tumors* / genetics
  • Gastrointestinal Stromal Tumors* / pathology
  • Gene Expression / genetics
  • Humans
  • Imatinib Mesylate* / pharmacology
  • Imatinib Mesylate* / therapeutic use
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Long Noncoding* / physiology
  • Signal Transduction* / genetics
  • Up-Regulation / genetics

Substances

  • Imatinib Mesylate
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Antineoplastic Agents
  • Fibronectins
  • MicroRNAs
  • MIRN200 microRNA, human
  • Microfilament Proteins
  • Phosphatidylinositol 3-Kinase