Oncotarget

Priority Research Papers:

A negative feedback regulatory loop between miR-138 and TP53 is mediated by USP10

Zhenghua Luo, Manchao Zhang, Ri Cui, Esmerina Tili, Taewan Kim, Tae Jin Lee, Yong Peng _ and Carlo Croce _

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Oncotarget. 2019; 10:6288-6296. https://doi.org/10.18632/oncotarget.27275

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Abstract

Zhenghua Luo1, Manchao Zhang1, Ri Cui1, Esmerina Tili1, Taewan Kim1, Tae Jin Lee1, Yong Peng2 and Carlo Croce1

1 Department of Cancer Biology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA

2 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China

Correspondence to:

Carlo Croce,email: carlo.croce@osumc.edu
Yong Peng,email: yongpeng@scu.edu.cn

Keywords: TP53; USP10; miR-138

Received: April 09, 2019     Accepted: September 10, 2019     Published: October 29, 2019

ABSTRACT

TP53 is a critical tumor suppressor. In approximately 50% of human cancers the TP53 gene is either lost or mutated. The expression level of TP53 in the cells is tightly controlled by a fine-tune machinery, mainly through the Mdm2-mediated ubiquitination pathway. On the other side, the ubiquitinated TP53 could be reversed and stabilized by USP7 and USP10, to keep the amount of TP53 in check. MicroRNAs can negatively regulate TP53 expression levels through direct targeting or positively regulate TP53 function through the repression of negative regulators of TP53. Here we report that microRNA-138 controls TP53 expression by directly targeting USP10. Furthermore, TP53 represses microRNA-138 expression, forming a negative feedback regulatory loop. This finding adds another layer of complexity to the TP53 network.


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