HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

Journal of Experimental & Clinical Cancer Research

Yayuan Wang¹  Yanjuan Song¹  Fengxia Liang¹  Minfeng Zhou²  Huarong Li²  Guangtao Pan²  Man Hu²  Jinxiao Li²  Rui Chen²  Zhaomin Yu³  Qian Yan⁴  Na Liu⁵ 

[1] College of Acupuncture & Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, 430060, Wuhan, China;Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, 430022, Wuhan City, Hubei Province, China;Department of oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, 430071, Wuhan, China;First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, 510405, Guangzhou, China;Rehabilitation Department of traditional Chinese Medicine, Union Red Cross Hospital, 430015, Wuhan, China;

关键词: Colorectal cancer;    Histone deacetylase 3;    MicroRNA-296-3p;    Thymine-guanine-interacting factor 1;    Transforming growth factor β signaling pathway;    Invasion;    Migration;   

DOI  :  10.1186/s13046-020-01720-w

来源: Springer

【 摘 要 】

BackgroundThe mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor β-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC.MethodsTo demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFβ axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining.ResultsHigher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression.ConclusionThis study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.

【 授权许可】

CC BY