lncRNA TMPO antisense RNA 1 promotes the malignancy of cholangiocarcinoma cells by regulating let-7g-5p/ high-mobility group A1 axis

Bioengineered. 2022 Feb;13(2):2889-2901. doi: 10.1080/21655979.2022.2025700.

Abstract

Cholangiocarcinoma (CHOL) is often diagnosed at an advanced stage; therefore, exploring its key regulatory factors is important for earlier diagnosis and treatment. This study aimed to identify the mechanisms of long non-coding RNA (lncRNA) TMPO Antisense RNA 1 (TMPO-AS1), microRNA let-7 g-5p, and high-mobility group A1 (HMGA1) proteins in CHOL. Our results, through quantitative real-time PCR and Western blot detection, showed that TMPO-AS1 and HMGA1 were overexpressed while let-7 g-5p was underexpressed in CHOL. Cell function experiments in CHOL cells revealed that TMPO-AS1 knockdown inhibited cell proliferation, colony formation, and cell migration, but induced apoptosis. TMPO-AS1 knockdown also suppressed tumor growth in vivo. Together with luciferase assay and Western blotting, we found that TMPO-AS1 could sponge let-7 g-5p to promote HMGA1 expression. Moreover, HMGA1 overexpression attenuated the effect of TMPO-AS1 downregulation in CHOL cells. Overall, our findings identified the oncogenic effect of TMPO-AS1 on CHOL cells, which may put forward a novel methodology for CHOL diagnosis and therapy.

Keywords: Cholangiocarcinoma; HMGA1; TMPO-AS1; let-7g-5p.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HMGA1a Protein / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • RNA, Antisense / physiology
  • RNA, Long Noncoding / physiology
  • Thymopoietins / antagonists & inhibitors
  • Thymopoietins / genetics*

Substances

  • HMGA1 protein, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Antisense
  • RNA, Long Noncoding
  • Thymopoietins
  • mirnlet7 microRNA, human
  • HMGA1a Protein
  • TMPO protein, human

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.