MicroRNA-454 inhibits the malignant biological behaviours of gastric cancer cells by directly targeting mitogen-activated protein kinase 1
Authors: Xiaodong Wang
Ying Song
Baichun Liu
Fuxing Wen
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; microRNAs; miR-454; biomarkers; prognosis
Affiliations: Department of Digestive Endoscopy, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China., Department of General Medicine, The General Hospital of China National Petroleum Corporation in Jilin, Jilin 132021, P.R. China.

Abstract:  Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer‑related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA‑454 (miR‑454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR‑454 in GC remain unclear and require further investigation. In the present study, we assessed miR‑454 expression in GC tissues and cell lines. We also explored the effects of miR‑454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR‑454. The results revealed that miR‑454 was significantly downregulated in GC tissues and cell lines. Low miR‑454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR‑454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen‑activated protein kinase 1 (MAPK1) was identified as a direct target of miR‑454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR‑454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR‑454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour‑suppressive effects of miR‑454 in GC. Collectively, our data demonstrated that miR‑454 may play tumour‑suppressing roles in GC through the regulation of MAPK1, suggesting that miR‑454 may be a novel biomarker and therapeutic target for patients with this disease. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 5D, 6D.  The effect of miR-454 on the apoptosis of MGC-803 and AGS cells was examined with flow cytometry analysis ;  The effects of MAPK1 underexpression on MGC-803 and AGS cell ... apoptosis were explored using ... flow cytometry analysis ;  Cell ... apoptosis were assessed in MGC-803 and AGS cells transfected with miR-454 mimics with or without pcDNA3.1-MAPK1 by ... flow cytometry analysis . ![file] The panel marked with a bright pink rectangle has a match in Figs 2D, 5D, 6D of [Zhao et al (2018)] . ![file] ![file] ------------------------------------------- UPDATE: Black-boxed panel has a match in Figs 2D, 5D, 6E of [Wang et al (2019)] . ![file] , 
 Figs 3D, 4B, 5A: ![file] This style of Western Blot was common in the productions of the [ Direct Target papermill] in 2017-2018. Here. for instance, Figs 3D, 4A, 5A from [Lv Wang (2018)] (Retracted; one author in common): ![file] , 
 Retracted [31 January 2022] .  Following the publication of this paper, the authors have been unable to obtain consistent results after having repeated some of the flow cytometric assay experiments, undermining their confidence in the reported conclusions concerning the regulatory action of miRu2011454 on gastric cancer cell apoptosis. Consequently, owing to a lack of confidence in the presented data, the authors have requested that this paper be retracted from the journal. All authors agree with the retraction of this article, and apologize to the Editor and readership for the inconvenience caused.  , 
 Three duplicated panels spread across - Fig 5C from  MicroRNAu201118b acts as an oncogene in gastric cancer by directly targeting Kruppelu2011like factor 6 ([Luo et al 2019] ). - **Fig 6C**. - Fig 6E from  MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4 ([Mao et al 2017] ). ![file] , 
 Dead-horse flogging will continue until morale improves. 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 from  MicroRNAu2011466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin ([Jia et al 2018] ). - **Fig 6C**. - 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] ,