J Cancer 2022; 13(6):1923-1932. doi:10.7150/jca.66914 This issue

Research Paper

Histone deacetylase (HDAC) 11 inhibits matrix metalloproteinase (MMP) 3 expression to suppress colorectal cancer metastasis

Yuqing Wen1,2,3, Xuemei Zhang4, Xiayu Li1, Li Tian1, Shourong Shen1, Jian Ma1,2,3, Feiyan Ai1,2,3✉

1. Department of Gastroenterology, the Third Xiangya Hospital, Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
2. Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, China.
3. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, NHC Key Laboratory of Carcinogenesis, Changsha, China.
4. Department of Pathology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.

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Citation:
Wen Y, Zhang X, Li X, Tian L, Shen S, Ma J, Ai F. Histone deacetylase (HDAC) 11 inhibits matrix metalloproteinase (MMP) 3 expression to suppress colorectal cancer metastasis. J Cancer 2022; 13(6):1923-1932. doi:10.7150/jca.66914. Available from https://www.jcancer.org/v13p1923.htm

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Abstract

Graphic abstract

Emerging evidence has implicated invasion and metastasis are the major common reason of treatment failure and the leading cause of death in colorectal cancer (CRC). Many members of the HDAC family have been reported to be key factors in the genesis and progression of cancer. Until now, few research focused on the actual expression patterns of HDAC11 in most malignancies. In the current study, we found that the expression of HDAC11 is decreased in mouse colitis tissues and colitis-associated cancer (CAC) tissue compared with normal colon tissue. Clinically HDAC11 expression is significantly lower in colorectal cancer tissues of patients and correlated with lymph node metastasis. Additionally, HDAC11 is downregulated in the relative high metastatic potential colorectal cancer cells. We also found HDAC11 inhibits the migration and invasion of colorectal cancer cell by downregulating Mmp3 expression. At the molecular level, the expression of HDAC11 inversely correlated with the level of histone H3K9 and H3K14 acetylation. In addition, analysis of chromatin-protein association by ChIP-qPCR demonstrated that the level of H3K9 acetylation correlated with the upregulation of Mmp3. Through a better understanding of this previously unknown role of HDAC11 in migration and invasion of colorectal cancer, HDAC11 may become a novel candidate for developing rational therapeutic strategies.

Keywords: HDAC11, colorectal cancer, invasion and metastasis, MMP3, H3K9ac