The LncRNA FGD5-AS1/miR-497-5p axis regulates septin 2 (SEPT2) to accelerate cancer progression and increase cisplatin-resistance in laryngeal squamous cell carcinoma

Mol Carcinog. 2021 Jul;60(7):469-480. doi: 10.1002/mc.23305. Epub 2021 May 18.

Abstract

Aberrant expression or mutation of the Septin gene family is closely associated with cancer progression, and septin 2 (SEPT2) exerts its tumor-promoting effects in multiple cancers, but its role in regulating laryngeal squamous cell carcinoma (LSCC) progression and drug resistance has not been investigated. Based on the published data, the present study identified that SEPT2 promoted cancer progression and increased cisplatin-resistance in LSCC, and a novel LncRNA FGD5-AS1/miR-497-5p axis was crucial for this process. Mechanistically, SEPT2 tended to be enriched in LSCC tissues and cells, and knock-down of SEPT2 inhibited cell proliferation, viability, migration, and tumorigenesis in LSCC cells in vitro and in vivo. Aside from that, SEPT2 overexpression increased cisplatin resistance in LSCC cells. Next, by conducting the dual-luciferase reporter gene system assay, we identified that the LncRNA FGD5-AS1/miR-497-5p axis regulated SEPT2 in LSCC. Specifically, LncRNA FGD5-AS1 sponged miR-497-5p to upregulate SEPT2 in LSCC cells in a competing endogenous RNA (ceRNA) mechanisms-dependent manner. Interestingly, upregulated LncRNA FGD5-AS1 and downregulated miR-497-5p were observed in LSCC tissues and cells, and LncRNA FGD5-AS1 ablation inhibited cancer progression. Also, LncRNA FGD5-AS1 overexpression increased cisplatin-resistance in LSCC by modulating the miR-497-5p/SEPT2 axis. Collectively, we conclude that targeting the LncRNA FGD5-AS1/miR-497-5p/SEPT2 signaling cascade may be an alternative strategy to treat LSCC in the clinic.

Keywords: LncRNA FGD5-AS1; cancer biology; laryngeal carcinoma; miR-497-5p; septin 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Septins / genetics*
  • Septins / metabolism
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • MIRN497 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SEPTIN2 protein, human
  • Septins
  • Cisplatin