MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/β-catenin signaling through targeting BCL9
Authors: Tianxiang Chen
Yongshen Niu
Zhikui Liu
Bowen Yao
Yazhao Li
Liang Wang
Qingguang Liu
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: BCL9; hepatocellular carcinoma; hypoxia; miR-3194-3p; β-catenin.
Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China;, Translational Medicine Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Abstract:  Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating β-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/β-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 Figures 5E and 9D appear to have a repeated image, although the brightness differs. Note: The last authors email address is all numerical, something that has been seen from papermill papers in the past. *** ![file] *** ![file] , 
 Correction, [10 August 2021] .  After publication of this article, the authors reached out to the Publisher to request correction to Figure 9(D). The authors confirmed that during the preparation of their manuscript, the image used in Figure 5(E) was re-used in error in Figure 9(D). A correction has been made to the article as follows: Figure 9. miR-3194-3p is down-regulated by hypoxia and mediates the promoting effects of hypoxia on metastasis and EMT of HCC cell. (A) u03b2-catenin protein levels in HCC cells transfected with miR-3194-3p inhibitor or miR-3194-3p over-expression vectors. (B) The expression level of HIF-1u03b1 in different time points in hypoxia condition. (C) The expression level of miR-3194-3p in Hep3B cells cultured in normoxia and hypoxia. (D) Transwell assays for Hep3B cells in normoxia and Hep3B cells and Hep3B cells transfected with miR-3194-3p in hypoxia. **pu2009 u2009.01. (E) The expression of BCL9, E-cadherin, N-cadherin and Vimentin of Hep3B cells in normoxia and Hep3B cells and Hep3B cells transfected with miR-3194-3p in hypoxia. *pu2009 u2009.05. nu2009=u2009six independent experiments. ![] , 
 At least one image in this paper seems to overlap with an image in another paper, after rotation and changes in coloring. Astute readers will note that the fields of view are different, suggesting that whomever prepared these figures had access to a full-sized image from which these figures were constructed. I did not see any overlap in authorship, although there seems to be a common institutional affiliation. These elements are sometimes seen in papers that have been outsourced. Figure 6D Artificial Cells Nanomedicine and Biotechnology (2019) doi: 10.1080 21691401.2019.1670190 https: pubpeer.com publications 8CDC6E6338DB3908698A528D4296E5 Figure 2d Cancer Cell International (2020) doi: 10.1186 s12935-020-01307-7 https: pubpeer.com publications 3B8DCF5FD243DBE29DE44124726673 *** ![file] *** Original placement ![file] , 
 From the Department of Unexpected Overlaps: - *[left]* Fig 10c from  Long non-coding RNA AGAP2-AS1, functioning as a competitive endogenous RNA, upregulates ANXA11 expression by sponging miR-16-5p and promotes proliferation and metastasis in hepatocellular carcinoma ([Liu et al 2019] ). - *[right]* **Fig 5E**. ![file] , 
 Unexpected similarities between Western Blot bands here and in  MicroRNA-1468 promotes tumor progression by activating PPAR-u03b3-mediated AKT signaling in human hepatocellular carcinoma ([Liu et al 2018] ). Fig 6E; Fig 7g from Liu et al (2018). ![file] Fig 6F; Fig 8f from Liu et al (2018). ![file] , 
 Unexpected similarities between Western Blot bands here and in  LncRNA OIP5-AS1 loss-induced microRNA-410 accumulation regulates cell proliferation and apoptosis by targeting KLF10 via activating PTEN PI3K AKT pathway in multiple myeloma ([Yang et al 2017] ). Here, Fig 3A and Fig 3e from Yang et al (2017). ![file] , 
 Dear Hoya camphorifolia, Thank you for your comment. Our investigation determined that all the experiments of this paper were finished by the first author and the images were manipulated. Based on these results, all authors have agreed to the retraction of this article from Artificial Cells, Nanomedicine, and Biotechnology. Thanks. , 
 #6 Dear Hoya camphorifolia, Thank you for your comment. Our investigation determined that all the experiments of this paper were finished by the first author and the images were manipulated. Based on these results, all authors have agreed to the retraction of this article from Artificial Cells, Nanomedicine, and Biotechnology. Thanks. , 
 Retracted [27 July 2022] . ------------------------ We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article: Bowen Yao, Yazhao Li, Liang Wang, Tianxiang Chen, Yongshen Niu, Qingguang Liu Zhikui Liu (2019) MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt u03b2-catenin signaling through targeting BCL9. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 3885u20133895, DOI: 10.1080 21691401.2019.1670190 Since publication, concerns have been raised about the integrity of the data in the article. In particular, Figures 3A, 5E, 6E and 6F appear to have been previously published in other journals with different author lists, specifically: - Figure 3A appears to have been duplicated with Figure 3E, Yang et al., Cell Death Disease (2017), DOI: 10.1038 cddis.2017.358 - Figure 5E appears to have been duplicated with Figure 10C, Liu et al., Journal of Experimental Clinical Cancer Research (2019), DOI: 10.1186 s13046-019-1188-x - Figure 6E and 6F appear to have been duplicated with Figure 10G and 10F, Liu et al., Journal of Experimental Clinical Cancer Research (2018), DOI: 10.1186 s13046-018-0717-3 When approached for an explanation, the authors checked their data and confirmed there are fundamental errors present and that the images had been u201cmanipulatedu201d. Therefore, they have agreed to the retraction of this article. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetracted.u201d ,