SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

Abstract

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

• Authors: Shi-Lan Zhang, Xiao Du, Lin-Na Tan, Fei-Hong Deng, Bing-Yi Zhou, He-Jun Zhou, Hong-Yi Zhu, Yi Chu, De-Liang Liu, Yu-Yong Tan
• Journal: American journal of translational research (Am J Transl Res) Vol. 12 Issue 2 Pg. 602-611 ( 2020) ISSN: 1943-8141 [Print] United States
• PMID: 32194908 (Publication Type: Journal Article)
• Copyright: AJTR Copyright © 2020.