HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway

Int J Biol Sci. 2022 May 27;18(9):3777-3794. doi: 10.7150/ijbs.70546. eCollection 2022.

Abstract

Competing endogenous RNAs (ceRNAs) are a newly discovered class of molecular regulators involved in many diseases, especially tumors. Therefore, exploration of the potential ceRNA regulatory network regarding the occurrence and development of pancreatic cancer will provide a new theoretical basis for its diagnosis and treatment. Based on the above background, we applied a bioinformatics approach to mine the public database The Cancer Genome Atlas (TCGA) and performed a series of subsequent molecular biology assays to confirm the hypothesis that HOXA10-AS/ miR-340-3p/HTR1D axis could modulate the malignant progression of pancreatic cancer. Here, our present study demonstrated that the expression level of HTR1D, positively correlated with the level of lncRNA HOXA10-AS and negatively associated with the level of miR-340-3p, was significantly increased in pancreatic cancer cell lines (PCs) compared with that in normal HPDE6-C7 cells. Knocking down HTR1D obviously inhibited the proliferation and migration of PCs and promoted apoptosis by upregulating p-AKT. Elevated miR-340-3p blocked the progression of pancreatic cancer by downregulating HTR1D. Lessened level of lncRNA HOXA10-AS reduced the sponging of miR-340-3p, resulting in an increase of miR-340-3p and a subsequent decrease of HTR1D to ultimately suppress the malignant biological behaviors of cancer. These data illustrated that the HOXA10-AS/miR-340-3p/HTR1D ceRNA axis acted a crucial part in the malignant biological behavior of pancreatic cancer in an AKT-dependent manner.

Keywords: HOXA10-AS; HTR1D; ceRNA; miR-340-3p; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Homeobox A10 Proteins
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Receptor, Serotonin, 5-HT1D / metabolism*
  • Signal Transduction

Substances

  • Homeobox A10 Proteins
  • MIRN340 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptor, Serotonin, 5-HT1D
  • HOXA10 protein, human
  • Proto-Oncogene Proteins c-akt