Long noncoding RNA FAM201A mediates the metastasis of lung squamous cell cancer via regulating ABCE1 expression

Eur Rev Med Pharmacol Sci. 2019 Dec;23(23):10343-10353. doi: 10.26355/eurrev_201912_19672.

Abstract

Objective: Long noncoding RNA (lncRNA) family with sequence similarity 201-member A (FAM201A) is a novel lncRNA promoting the development of various cancers. However, the biological function of FAM201A on the metastasis of lung squamous cell carcinoma (LSCC) remains unknown. The aim of this study was to explore the molecular mechanism of FAM201A and its target protein in advanced LSCC.

Patients and methods: Quantitative Polymerase Chain Reaction (qPCR) was applied to evaluate FAM201A expression in lung cancer tissues. The impact of high FAM201A expression on the overall survival in patients with lung cancer was tested using the log-rank test. The relevance between aberrant FAM201A and clinicopathological characteristics in patients with lung cancer was analyzed using the Chi-square tests. Cell proliferation was assayed using the Cell Counting Kit-8 (CCK-8) and a transwell assay, and the mice xenograft models were applied to determine the promoting effects of FAM201A on LSCC in vitro and in vivo. The underlying regulatory mechanism was explored through RNA transfection, qPCR, and Western blotting. The correlation between ATP-binding cassette transporter E1 (ABCE1) and FAM201A expression was verified using Spearman's correlation coefficient.

Results: FAM201A is aberrantly elevated in tissues from patients with non-small cell lung cancer. High levels of FAM201A expression were more likely to present in patients with squamous type, M1 stage, and inferior overall survival. Differential expression was found between non-metastatic and metastatic squamous carcinoma, but not in adenocarcinoma. FAM201A knockdown inhibits cell proliferation, migration, and invasion of LSCC cells in vitro, and represses tumor growth in vivo. Furthermore, ABCE1 in LSCC cells was downregulated by silencing FAM201A. The tissue level of ABCE1 was positively correlated with FAM201A expression in patients with LSCC.

Conclusions: FAM201A may markedly induce migration and invasion of LSCC, resulting in the M1 stage and poor survival. These findings suggest the FAM201A-ABCE1 axis as a novel therapeutic target in LSCC.

MeSH terms

  • ATP-Binding Cassette Transporters / biosynthesis
  • ATP-Binding Cassette Transporters / physiology*
  • Animals
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / physiopathology*
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / physiology*
  • Survival Analysis
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • ABCE1 protein, human
  • ATP-Binding Cassette Transporters
  • RNA, Long Noncoding