Long noncoding RNA ABHD11-AS1 predicts the prognosis of pancreatic cancer patients and serves as a promoter by activating the PI3K-AKT pathway

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8630-8639. doi: 10.26355/eurrev_201812_16627.

Abstract

Objective: Accumulating evidence showed aberrant expressions of long non-coding RNAs (lncRNAs) strongly correlated to the development of cancers, including pancreatic cancer (PC). Whether lncRNA ABHD11-AS1 (ABHD11-AS1) is involved in PC remains to be elucidated. Thus, we aimed to evaluate the effects of ABHD11-AS1 on PC and the underlying molecular mechanism.

Patients and methods: RT-PCR was used to detect the expression level of ABHD11-AS1 in both PC tissue and cell lines. Then, the correlation of ABHD11-AS1 expression with clinicopathological features and prognosis was studied. Cell proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, and transwell assays. We further investigated the effect of abnormal ABHD11-AS1 expression through the PI3K/AKT and EMT pathway by Western blot assays in treated PC cells.

Results: We found that the expression of ABHD11-AS1 was significantly increased in both PC tissues and cell lines. The clinical analysis revealed that a high level of ABHD11-AS1 expression was correlated with distant metastasis, TNM stage, and tumor differentiation. The Kaplan-Meier analysis showed that high ABHD11-AS1 expression levels predicted poorer survival. Moreover, univariate and multivariate analyses confirmed that the expression of ABHD11-AS1 was an independent and significant factor associated with poor overall survival rates. Loss-of-function experiments showed that the knockdown of ABHD11-AS1 suppressed PC cell proliferation, migration, invasion, and EMT in vitro. Mechanistically, the knockdown of ABHD11-AS1 decreased phospho(p) AKT and phospho(p) PI3K expression, but did not affect the AKT and PI3K expression in PC cells CONCLUSIONS: This study suggested that ABHD11-AS1 may potentially function as a valuable prognostic biomarker and a therapeutic target for PC patients.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatectomy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt