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  • CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity.

CircPVT1 attenuates negative regulation of NRAS by let-7 and drives cancer cells towards oncogenicity.

Scientific reports (2021-04-29)
Joshua Miguel C Danac, Reynaldo L Garcia
ABSTRACT

Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3'UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Goat Anti-Mouse IgG (H+L) Antibody, FITC conjugate, Upstate®, from goat
Sigma-Aldrich
Anti-GAPDH Mouse mAb (6C5), liquid, clone 6C5, Calbiochem®
Sigma-Aldrich
Goat Anti-Rabbit IgG (H+L) Antibody, FITC conjugate, Upstate®, from goat