Circ_0000284 upregulates RHPN2 to facilitate pancreatic cancer proliferation, metastasis, and angiogenesis through sponging miR-1179

J Biochem Mol Toxicol. 2023 Mar;37(3):e23274. doi: 10.1002/jbt.23274. Epub 2022 Dec 19.

Abstract

Background: Circular RNA (circRNA) has been confirmed to be a key regulator for pancreatic cancer (PC) progression, but the role of circ_0000284 in PC development remains unclear.

Methods: Quantitative real-time PCR was used to measure the expression of circ_0000284, microRNA (miR)-1179, and rhophilin 2 (RHPN2). PC cell proliferation, metastasis, angiogenesis, and apoptosis were assessed by EdU assay, transwell assay, tube formation assay, and flow cytometry. Relative protein expression was determined by western blot analysis. The interaction between miR-1179 and circ_0000284 or RHPN2 was confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results: Circ_0000284 was significantly upregulated in PC tissues and cells, and its knockdown inhibited PC cell proliferation, migration, invasion, and angiogenesis while promoting apoptosis. MiR-1179 was downregulated in PC tissues and cells, and it could be sponged by circ_0000284. Moreover, the miR-1179 inhibitor reversed the regulation of circ_0000284 knockdown on PC cell progression. The highly expressed RHPN2 was found in PC tissues and cells, and it could be targeted by miR-1179. Also, circ_0000284 sponged miR-1179 to regulate RHPN2 expression. Overexpressed RHPN2 could reverse the regulation of circ_0000284 knockdown on PC cell progression. In addition, interference of circ_0000284 was discovered to repress PC tumor growth by regulating miR-1179/RHPN2.RHPN2.

Conclusion: To sum up, our data confirmed that circ_0000284 facilitated PC malignant progression depending on the regulation of miR-1179/RHPN2 axis, suggesting that circ_0000284 might be a potential target for PC treatment.

Keywords: RHPN2; circ_0000284; miR-1179; pancreatic cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Cell Proliferation
  • Humans
  • MicroRNAs*
  • Pancreas
  • Pancreatic Neoplasms*

Substances

  • MicroRNAs
  • RHPN2 protein, human
  • Adaptor Proteins, Signal Transducing