MicroRNA-195 functions as a tumor suppressor by inhibiting CBX4 in hepatocellular carcinoma
Authors: Changli Zheng
Jianda Zhou
Wei Liu
Qi Wang
Qinghai Zeng
Xiaowei Peng
Jingjing Li
Rui Liu
Ke Cao
Peiguo Cao
Chenghui Huang
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNA-195; tumor metastasis; angiogenesis; hepatocellular carcinoma; chromobox homolog 4
Affiliations: Department of Pathology, Xiangya Basic Medical College, Central South University, Changsha, Hunan 410013, P.R. China., Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China., Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China., Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China., Department of Head and Neck Surgery, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410006, P.R. China.

Abstract:  MicroRNA-195 (miR-195) plays important roles in tumor metastasis and angiogenesis, yet its function and mechanism of action in hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we aimed to confirm whether chromobox homolog 4 (CBX4) is a direct target gene of miR-195 and determine the functions of miR-195 through the CBX4 pathway. miR-195 expression was slightly lower in the HCC tissues compared with that in the adjacent normal tissues. In addition, western blotting and qRT-RCR results showed that both CBX4 mRNA and protein levels were downregulated upon miR-195 overexpression. Luciferase reporter assays revealed that CBX4 is a direct target gene of miR-195. Furthermore, overexpression of CBX4 significantly restored the proliferative, invasive and migratory capacities of the HepG2 cells. Finally, in vivo experiments confirmed that high expression of CBX4 in HepG2 cells promoted tumor growth. In conclusion, our study demonstrated that miR-195 acts as a tumor suppressor by directly targeting CBX4 in HCC. This finding suggests a potential novel strategy for therapeutic interventions of this disease. 

Retracted: Yes

PubPeer comments:
 Fig 4D.  Representative microscopic images of invasive cells from the NC, miR-195 and miR-195+CBX4 groups . ![file] I set up a spreadsheet to include the various papers using this versatile suite of Transwell images to represent all possible combinations of cell-lines and treatments. This is the 44th manifestation. For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid . ![] Figs 4D, 6D from [Xia et al (2016)] . ![] Also *[above]* Fig 4C from [Lai, Chen Li (2015)] .  a Transwell assay were performed to examine the cell proliferation of AGS cells transfected with miR-133a mimics, miR-133a inhibitor, or co-transfected with miR-133a mimics and FSCN1 plasmid. Control: AGS cells without any transfection. *[below]* Figs 3(B), 6(B) from [Shi et al (2015)] .  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with NC scramble miRNA or miR-204 mimics, respectively. Control, Saos-2 and U-2 OS cells without any transfection ...  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with Sirt1 siRNA or co-transfected with miR-204 mimics and the Sirt1 plasmid, respectively. Control, Saos-2 and U-2 OS cells without any transfection . ![file] , 
 Retracted [16 July 2021] . ------------------------- Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 4D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Oncology Reports*, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. ,