HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis
Authors: Yanjuan Song
Yayuan Wang
Qian Yan
Fengxia Liang
Minfeng Zhou
Guangtao Pan
Huarong Li
Na Liu
Rui Chen
Jinxiao Li
Man Hu
Zhaomin Yu
Journal: Journal of Experimental & Clinical Cancer Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; Histone deacetylase 3; Invasion; MicroRNA-296-3p; Migration
Affiliations: Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan City, 430022, Hubei Province, China., Rehabilitation Department of traditional Chinese Medicine, Union Red Cross Hospital, Wuhan, 430015, China., Department of oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, 430071, China., First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, China., College of Acupuncture & Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan, 430060, China., College of Acupuncture & Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan, 430060, China. ., Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Avenue, Wuhan City, 430022, Hubei Province, China. .

Abstract:  Background: The 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. Methods: To 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&amp;E staining and TUNEL staining. Results: Higher 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. Conclusion: This 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. 

Retracted: No

PubPeer comments:
 *[left]* Fig 2E.  Representative images of xenograft tumors derived from **SKOV3** cells stable expressing miR-363 and miR-NC . *[right]* Fig 6C from [Lin et al (2017)] .  representative image of [**TPC-1**] tumor were shown . ![file] No authors in common, though both research groups are affiliated to Jilin University. , 
 From the Department of Unexpected Similarities: *[above]* Fig 5D.  Estimation of number of colonies in SKOV3 cells stable expressing miR-363 or miR-NC transfected with NOB1 plasmid without 3u2019UTR . *[below]* Fig 2C from [Li et al (2018)] .  The colony formation assay showed the effect of miR-361-5p on TPC-1 cell colony formation . ![file] , 
 *[left]* Fig 2C.  Estimation of colonies in SKOV3 cells stable expressing miR-363 and miR-NC . *[right]* Fig 2C from [Fei et al (2019)] .  Colony formation assay was employed to evaluate the effect of ROR knockdown on U2OS cell colony formation. ![file] Quite different experiments, no authors in common, a panel shared in common. However, the repeated details on other panels cast suspicion on the authenticity of these images. , 
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