Long noncoding RNA HOXA11-AS promotes gastric cancer cell proliferation and invasion via SRSF1 and functions as a biomarker in gastric cancer

World J Gastroenterol. 2019 Jun 14;25(22):2763-2775. doi: 10.3748/wjg.v25.i22.2763.

Abstract

Background: Gastric cancer (GC) is the fourth most frequent malignancy all over the world. The diagnosis of GC is challenging and the prognosis of GC is very unfavorable. Accumulating evidence reveals that serum long noncoding RNAs (lncRNAs) can function as biomarkers in various types of cancers, including GC.

Aim: To explore the level and molecular mechanism of the lncRNA HOXA11-AS in GC and the diagnostic and prognostic significance of serum HOXA11-AS in GC.

Methods: HOXA11-AS levels in GC tissue, cell lines, and serum samples were measured. The correlation between HOXA11-AS expression and clinicopathological characteristics was analyzed. The role of HOXA11-AS in the diagnosis and prognosis of GC was evaluated. Cell function assays were performed for exploration of the roles of HOXA11-AS in GC cells. Moreover, Western blot was performed to explore the target regulated by HOXA11-AS in GC cells.

Results: Up-regulation of HOXA11-AS was found in GC tissues, cell lines, and serum samples. In GC patients, decreased serum HOXA11-AS levels were negatively related with tumor size, TNM stage, and lymph node metastasis. The area under the receiver operating characteristic curve of serum HOXA11-AS in the diagnosis of GC was 0.924 (95%CI: 0.881-0.967; sensitivity, 0.787; specificity 0.978). Results of the Kaplan-Meier survival curves suggested the GC patients with a lower HOXA11-AS level having a better overall survival rate. HOXA11-AS promoted GC cell proliferation and invasion. SRSF1 may be the target regulated by HOXA11-AS in GC cells.

Conclusion: HOXA11-AS promotes GC cell proliferation and invasion via SRSF1 and may function as a promising marker in GC.

Keywords: Biomarker; Gastric cancer; HOXA11-AS; Long noncoding RNA; SRSF1.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / metabolism*
  • Serine-Arginine Splicing Factors / genetics*
  • Stomach / pathology
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Survival Rate
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Cell-Free Nucleic Acids
  • RNA, Long Noncoding
  • SRSF1 protein, human
  • Serine-Arginine Splicing Factors