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Int J Clin Exp Pathol 2013;6(5):870-877

Original Article
RNAi screening identifies KAT8 as a key molecule important for cancer cell survival

Shuang Zhang, Xianhong Liu, Yong Zhang, Ying Cheng, Yang Li

Department of Pathophysiology, Norman Bathune College of Medical Sciences, Jilin University, Changchun, China; The first Department of
Internal Medicine, Jilin Province Cancer Hospital, Changchun, China. Equal contribution.

Received February 16, 2013; Accepted April 1, 2013; Epub April 15, 2013; Published May 1, 2013

Abstract: Histone acetyltransferases (HATs) regulate many critical cancer events, including transcriptional regulation of oncogene and tumor
suppressors, chromatin structure and DNA damage response. Abnormal expression of HATs has been reported in a number of cancers.
However, cellular functions of HATs in cancer and molecular mechanisms remain largely unclear. Here, we performed a lentiviral
vector-mediated RNAi screen to systematically address the function of HATs in lung cancer cell growth and viability. We identified 8 HATs
genes involved in A549 cell viability. Further experiments showed that KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1
signaling. Moreover, KAT8 inhibition led to p53 induction and subsequently reduced bcl-2 expression. Our results demonstrate an important
role of KAT8 in cancer and suggest that KAT8 could be a novel cancer therapeutic target. (IJCEP1302018).

Keywords: HATs, RNAi screen, KAT8, cyclin D1, p53, cell survival

Address correspondence to: Dr. Yang Li, Department of Pathophysiology, Norman Bathune College of Medical Sciences, Jilin University,
Changchun, China. E-mail: lyang@jlu.edu.cn or chengying@csco.org.cn