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Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway

Authors Zhang SL, Zhu HY, Zhou BY, Chu Y, Huo JR, Tan YY, Liu DL

Received 17 November 2018

Accepted for publication 1 March 2019

Published 2 April 2019 Volume 2019:12 Pages 2409—2419

DOI https://doi.org/10.2147/OTT.S194986

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Carlos E Vigil


Shi-Lan Zhang, Hong-Yi Zhu, Bing-Yi Zhou, Yi Chu, Ji-Rong Huo, Yu-Yong Tan, De-Liang Liu

Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration.
Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients’ clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored.
Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression.
Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

Keywords: colon cancer, cell growth and migration, histone deacetylase 6, MAPK/ERK pathway, CRC prognosis

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