Long non-coding RNA MT1DP shunts the cellular defense to cytotoxicity through crosstalk with MT1H and RhoC in cadmium stress

• DOI: 10.1038/s41421-017-0005-y
• Publication Date: 2018-01-23T12:26:49Z
• Authors: Ming Gao; Minjun Chen; Changying Li; Ming Xu; Yun Liu; Min Cong; Nan Sang; Sijin Liu
• Keywords: Crosstalk; RhoC

Metallothioneins (MTs) are known to protect cells against oxidative stress, especially providing protection cadmium (Cd) toxicity in hepatocytes. There various gene variants and pseudogenes for MTs; however, there is little understanding on the functions of those non-coding MT members that be expressed as long RNAs (lncRNAs) nowadays. Different from most protein-coding members, MT1DP was here found remarkably induced provoke cytotoxicity hepatocytes response Cd treatment. exerted such a pro-apoptotic function Cd-treated through interacting with two partners: RhoC MT1H. On one hand, interacted protein increase latter's stability by preventing lysosome-dependent degradation. Therefore, upon MT1DP/RhoC complex quickly reinforced activate RhoC-CCN1/2-AKT signaling potentiate Ca2+ influx, leading enhanced uptake elevated toxicity. other MT1H, member family function, respond exposure along MT1DP. Mechanistically, MT1H were uncovered mutually each reciprocal ceRNA mechanism, building up positive feedback loop enforce MT1DP-conducted exposure. Moreover, contribute much more activation than Considered together, we unveiled mystery whether pseudogene within family, MT1DP, has actual biological regulating Cd-induced cellular defense. Our findings unearthed an important role calibrating machinery switch defense crosslinking interplay between its partners, namely RhoC, under stress.