(699.16) Bioengineered miR-34a targets MPV17L2 to control cancer cell mitochondrial functions

Poster Board Number: B129

Meijuan Tu (UCDAVIS), Wanrong Yi (UCDAVIS), Ai-Xi Yu ( Zhongnan Hospital of Wuhan University), Jun Lin ( Zhongnan Hospital of Wuhan University), Ai-Ming Yu (UCDAVIS)

MicroRNAs (miRNA or miR) are small noncoding RNAs derived from the genome to control posttranscriptional gene expression critical for various cellular processes. Recently we have invented a novel platform technology that offers high-yield production of humanized, bioengineered miRNA agents (hBERAs) for research and development. This study is aimed to produce and utilize a novel biologic miR-34a-5p (or miR-34a) molecule, namely hBERA/miR-34a, to delineate the role of miR-34a-5p in the regulation of mitochondrial functions in carcinoma cells. Bioengineered hBERA/miR-34a was selectively processed to target miR-34a-5p in human osteosarcoma and lung cancer cells. The mitochondrial inner membrane protein MPV17 like 2 (MPV17L2) was identified and validated as a new direct target for miR-34a-5p. Furthermore, we demonstrated that miR-34a-5p-controlled MPV17L2 protein downregulation significantly inhibited respiratory chain complex I assembly and activities as well as intracellular ATP levels. Consequently, biologic miR-34a-5p treatment sharply reduced cancer cell mitochondrial respiration, increased oxidative stress, and elevated apoptotic cell death. These results demonstrate an important role of miR-34a-5p-MPV17L2 pathway in the control of mitochondrial functions in carcinoma cells and support the utility of novel bioengineered miRNA molecules for functional studies.

Support or Funding Information

A-M Yu is supported by the National Cancer Institute (grant No. R01CA225958) and National Institute of General Medical Sciences (R35GM140835), National Institutes of Health. A-X Yu and J Lin are supported by Hubei Province Scientific and Technological Innovation Key Project (2019ACA136, China). W-R Yi is supported by the Fundamental Research Funds for the Central Universities (2042020kf0139). The authors also appreciate the access to the Molecular Pharmacology Shared Resources funded by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute (P30CA093373).