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TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma.

Cancer Cell. 2014; 
Hall DP, Cost NG, Hegde S, Kellner E, Mikhaylova O, Stratton Y, Ehmer B, Abplanalp WA, Pandey R, Biesiada J, Harteneck C, Plas DR, Meller J, Czyzyk-Krzeska MF.
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Gene Synthesis The TRPM3 shRNA-insensitive mutant was obtained by synonymous mutation of the shRNA binding site and replacement of the neomycin selection marker with a zeocin cassette in pcDNA3.1 (GenScript). Get A Quote

摘要

Autophagy promotes tumor growth by generating nutrients from the degradation of intracellular structures. Here we establish, using shRNAs, a dominant-negative mutant, and a pharmacologic inhibitor, mefenamic acid (MFA), that the Transient Receptor Potential Melastatin 3 (TRPM3) channel promotes the growth of clear cell renal cell carcinoma (ccRCC) and stimulates MAP1LC3A (LC3A) and MAP1LC3B (LC3B) autophagy. Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca(2+) and Zn(2+) fluxes inhibit miR-214, which directly targets LC3A and LC3B. The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-20... More

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