MicroRNA-21 activation of ERK signaling via PTEN is involved in arsenite-induced autophagy in human hepatic L-02 cells. (11th June 2016)

• Record Type: Journal Article
• Authors: Liu, Xinlu; Luo, Fei; Ling, Min; Lu, Lu; Shi, Le; Lu, Xiaolin; Xu, Hui; Chen, Chao; Yang, Qianlei; Xue, Junchao; Li, Jun; Zhang, Aihua; Liu, Qizhan
• Is Part Of: Toxicology letters. Volume 252(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-06-11
• Subjects: miRNA-21 -- Gene of phosphate and tension homology deleted on chromosome ten (PTEN) -- Extracellular regulated protein kinase (ERK) -- Autophagy -- Arsenite; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.04.015
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Elevated levels of miR-21 are associated with arsenite-induced autophagy in L-02 cells. miR-21-activated ERK signaling via inhibition of PTEN is involved in arsenite-induced autophagy in L-02 cells. Autophagy regulated by miR-21 via PTEN/ERK signaling is involved in arsenite-induced carcinogenesis. Abstract: Autophagy, an evolutionarily conserved cellular process, has diverse physiological and pathological roles in biological functions. Whether autophagy is induced by arsenite, a well-established human carcinogen, and the molecular mechanisms involved, remain to be established. Further, microRNAs (miRNAs) act as regulators in various cancers, but how miRNAs regulate autophagy remains largely unexplored. We have found that, in human hepatic epithelial (L-02) cells, arsenite increases levels of autophagy-related proteins in a concentration- and time-dependent manner and elevates the number of autophagic vacuoles (AVs). Arsenite also activates the ERK pathway in a dose- and time-dependent manner. In L-02 cells exposed to arsenite, microRNA-21 (miRNA-21) is over-expressed, and its target proteins, PTEN, PDCD4, and Spry1, are decreased. Moreover, inhibition of miR-21 increases levels of PTEN, and reduces levels of Beclin 1 and LC3 II/I, indicating that miR-21 is involved in arsenite-induced autophagy. In addition, ectopic expression of PTEN blocks the effect of miR-21 on the arsenite-induced autophagy and decreases p-ERK levels. Also, ERK promotes the autophagy induced by arsenite. In sum, upon exposure of cells to arsenite, over-expression of miR-21 activates ERK through PTEN, factors that participate in arsenite-induced autophagy. This link, mediated through miRNAs, establishes a mechanism for the development of autophagy that is associated with arsenic toxicity. Such information contributes to an understanding of the liver toxicity caused by arsenite.