Micrornas and Apoptosis in Cell Culture - Application for Enhanced Biological Production and Cancer Treatment

MicroRNAs and apoptosis in cell culture - application for enhanced biological production and cancer treatment.

Joseph Shiloach Aliaksandr Druz, Yu-Chi Chen Michael Betenbaugh, Rajarshi Guha, and Scott Martin

MicroRNAs are global regulators of gene expression that are involved in multiple cellular processes such as apoptosis, cell development, differentiation, metabolism, and proliferation. Simultaneous alteration of multiple pathways to modify cells performance may be possible by changing the miRNA expression profiles.  Two examples will be given; the first will describe the enhancement of recombinant protein production from CHO cells by the alteration of the expression profile of microRNAs involved in apoptosis regulation. In this case the inhibition of miR-466h expression caused a delay in apoptosis initiation, increased cell viability decreased Caspase-3/7 levels and contribute to higher recombinant protein expression. In the second example large-scale screening of the complete microRNA mimics library demonstrated that the human microRNA, hsa-miR-15a-3p, has a pro-apoptotic role in several human cancer cells. This novel member of the pro-apoptotic miRNA cluster, miR-15a/16, was found to cause viability loss in B/CMBA cells during preliminary screening. Microarrays and bioinformatics analysis showed that hsa-miR-15a-3p activates Caspase-3/7 and reduce cell viability by inhibiting the expression of bcl2l1 (bcl-x_L) in difference cell lines. It may therefore be considered for apoptosis modulating therapies in cancers associated with high Bcl-x_L expression (cervical, pancreatic, breast, lung, and colorectal carcinomas).

Stable inhibition of mmu-miR-466h-5p improves apoptosis resistance and protein production in CHO cells. Druz A, Son YJ, Betenbaugh M, Shiloach J.Metab Eng. 2013 Mar;16:87-94

Large-scale screening identifies a novel microRNA, miR-15a-3p, which induces apoptosis in human cancer cell lines. Druz A, Chen YC, Guha R, Betenbaugh M, Martin SE, Shiloach J.

RNA Biol. 2013 Feb;10(2):287-300.