CircDUSP22 Overexpression Restrains Pancreatic Cancer Development via Modulating miR-1178-3p and Downstream BNIP3

Yingqi Shi1, Meiqin Shen2, Yanmei Yang2

  • 1Department of Gastroenterology, Nantong First People's Hospital, No. 6 Haier Lane North Road, Nantong, 226000, Jiangsu, China. shiyq2016@163.com.

Biochemical Genetics
|September 5, 2022
PubMed

Insights

Circular RNA dual specificity phosphatase 22 (circDUSP22) is downregulated in pancreatic cancer (PaCa). Upregulating circDUSP22 inhibits PaCa cell growth and tumor development by targeting miR-1178-3p and BNIP3.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant circular RNA (circRNA) expression is linked to cancer development.
  • Many differentially expressed circRNAs lack functional characterization, hindering therapeutic strategies.
  • Pancreatic cancer (PaCa) remains a significant challenge with limited effective treatments.

Purpose of the Study:

  • To investigate the functional role of circRNA-dual specificity phosphatase 22 (circDUSP22) in pancreatic cancer (PaCa).
  • To elucidate the molecular mechanism underlying circDUSP22's action in PaCa progression.
  • To assess the potential of circDUSP22 as a therapeutic target for PaCa.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and western blotting for expression analysis.
  • In vitro assays (MTT, EdU, colony formation, flow cytometry) for cell proliferation, cell cycle, and apoptosis.
  • Dual-luciferase reporter and pull-down assays to confirm molecular interactions.
  • In vivo animal studies to evaluate therapeutic efficacy.

Main Results:

  • circDUSP22 expression was significantly decreased in PaCa tissues and cells.
  • Ectopic expression of circDUSP22 inhibited PaCa cell proliferation, arrested the cell cycle, and induced apoptosis.
  • circDUSP22 directly targeted miR-1178-3p, and miR-1178-3p targeted BNIP3, with both showing altered expression in PaCa.
  • circDUSP22 overexpression suppressed tumor growth in vivo, partly via the circDUSP22/miR-1178-3p/BNIP3 axis.

Conclusions:

  • circDUSP22 functions as a tumor suppressor in pancreatic cancer.
  • The circDUSP22/miR-1178-3p/BNIP3 pathway is a key regulator of PaCa progression.
  • circDUSP22 holds potential as a novel therapeutic target for pancreatic cancer treatment.