MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin
Authors: Desheng Tang
Xinchen Zhang
Yanhua Hu
Lei Yao
Chen Sun
Fujun Li
Chen Jia
Dequan Wu
Journal: Oncology Reports (2018)
Discipline: CLINICAL MEDICINE
Keywords: miRNA; hepatocellular carcinoma; HCC; miR-466; proliferation
Affiliations: Department of Liver Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Abstract:  Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA‑466 (miR‑466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumor‑suppressing roles of miR‑466 in HCC. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect miR‑466 expression in HCC tissues and cell lines. The effects of miR‑466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit‑8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR‑466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RT‑qPCR and western blot analysis. It was found that miR‑466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR‑466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR‑466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR‑466 level. Moreover, inhibition of MTDH displayed similar tumor‑suppressing roles as miR‑466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumor‑suppressor activity of miR‑466 overexpression in HCC cells. These findings suggest that miR‑466 is a potential therapeutic tool for HCC therapy. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 4C, 5C.  The apoptosis rate of Huh7 and Hep3B cells after transfection with miR-466 mimics or miR-NC was assessed using flow cytometric analysis ;  The ... apoptosis ...of Huh7 and Hep3B cells transfected with si-MTDH or si-NC were assessed by ...;, flow cytometry analysis ;  flow cytometric analysis ... were employed to determine the ... apoptosis ... of Huh7 and Hep3B cells cotransfected with miR-466 mimics and pcDNA3.1 or pcDNA3.1-MTDH . ![file] Light blue boxes mark panels with matches in Figs 2D, 5D of [Liu et al (2017)] . ![file] Dark green box marks panel with a match in Figs 2D,5D,6D of [Kang et al (2017)] . ![file] ![file] I did not search further for additional panel duplications. , 
 *[upper left]* Fig 5C from  MicroRNAu2011432 is downregulated in osteosarcoma and inhibits cell proliferation and invasion by directly targeting metastasisu2011associated in colon canceru20111 ([Lv et al 2018] ). *[upper right]* **Fig 5D**. *[middle]* **Fig 4D**. *[lower left]* Fig 5C from  MicroRNA-212 Targets Mitogen-Activated Protein Kinase 1 to Inhibit Proliferation and Invasion of Prostate Cancer Cells ([Hu et al 2018] ). *[lower right]* Fig 5E from  microRNA-605 inhibits the oncogenicity of non-small-cell lung cancer by directly targeting Forkhead Box P1 ([Zhou Li 2019] ) **[retracted]**. ![] , 
 Further unexpected similarities. *[above]* Fig 2E. *[below]* Fig 5E from  microRNA-769 is downregulated in colorectal cancer and inhibits cancer progression by directly targeting cyclin-dependent kinase 1 ([Wang et al 2018] ) **[retracted]**. ![file] , 
 Going back to Fig 5... *[upper left]* Fig 6D E from  MicroRNAu2011876u20115p inhibits the progression of glioblastoma multiforme by directly targeting Forkhead box M1 ([Wang et al 2018] ). *[upper right]* Fig 2C from  MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38 MAPK signalling pathways ([Zhang et al 2018] ). *[below]* **Fig 5D E**. ![file] , 
 #3 Clockwise from upper left: - Fig 5D E from  MicroRNAu2011876u20115p inhibits the progression of glioblastoma multiforme by directly targeting Forkhead box M1 ([Wang et al 2018] ); - Fig 2D E from  microRNA-769 is downregulated in colorectal cancer and inhibits cancer progression by directly targeting cyclin-dependent kinase 1 ([Wang et al 2018] ) **[retracted]**; - **Fig 2D E** again; - Fig 2F G from  LINC00511 promotes the malignant phenotype of clear cell renal cell carcinoma by sponging microRNA-625 and thereby increasing cyclin D1 expression ([Deng et al 2019] ). ![] , 
 Fig 5D yet again (below). Above, Fig 5D from  MicroRNAu2011539 inhibits cell proliferation, colony formation and invasion in pancreatic ductal adenocarcinoma by directly targeting IGFu20111R ([Lin et al 2018] ). ![file] H t ImageTwin. , 
 Multiple overlaps. From top to bottom: - Fig 4D from  MicroRNAu2011629 inhibition suppresses the viability and invasion of nonu2011small cell lung cancer cells by directly targeting RUNX3 ([Zhuang Cheng 2019] ). - **Fig 4E**. - Fig 6C from  MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1 ([Wang et al 2017] ) **[retracted]**. - Fig 4C from  Long Noncoding RNA SNHG7, a Molecular Sponge for microRNA-485, Promotes the Aggressive Behavior of Cervical Cancer by Regulating PAK4 ([Wu et al 2020] ) **[retracted]**. - Fig 2F from  Long noncoding RNA NR2F1-AS1 enhances the malignant properties of osteosarcoma by increasing forkhead box A1 expression via sponging of microRNA-483-3p ([Li et al 2019] ). ![file] , 
 Retracted [27 June 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the flow cytometric data shown in Figs. 2C, 4C and 5C, and the cell invasion assay data shown in Figs. 2D and E, 4D and E and 5D and E were strikingly similar to data appearing in different form in other articles by different authors. In addition, the authors independently contacted the Editorial Office to request that this paper be retracted owing to the fact that they had not obtained approval from the Ethics Committee of The Second Affiliated Hospital of Harbin Medical University to use the tissue samples, even though they had written that this study was approved by the Ethics Committee, and written informed consent had been provided by all patients enrolled in the research. 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, and the authors own admission of serious problems concerning the ethical nature of the study, the Editor has decided that this paper should be retracted from the Journal. The authors have agreed to the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,