MicroRNA‚Ä?37 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways
Authors: Xuerong Liu
Jinglong Zhao
Yan Wang
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Colorectal cancer; microRNA-337; KRAS; tumour suppressor; oncogenic genes
Affiliations: Department of Oncology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China., Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Abstract:  Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Tumour progression and development in CRC is a multi-step process involving a large number of genetic and epigenetic alterations. Previous studies indicated that abnormally expressed microRNAs play critical roles in CRC through regulation of oncogenic and tumour-suppressor genes. Hence, determination of the function of microRNAs may provide novel therapeutic targets for CRC diagnosis and treatments. MicroRNA‚Ä?37 (miR‚Ä?37) has been reported to be downregulated in several cancer types. However, the expression, function and underlying mechanisms of miR‚Ä?37 in CRC have not been clearly elucidated. In this study, miR‚Ä?37 was significantly decreased in CRC tissues and cell lines. Low miR‚Ä?37 expression level was correlated with lymph node metastasis, distant metastasis and TNM stage of CRC patients. In addition, upregulation of miR‚Ä?37 suppressed cell proliferation and invasion and promoted apoptosis in CRC. Based on bioinformatics analysis, we assumed that Kirsten rat sarcoma viral oncogene homolog (KRAS) was directly modulated by miR‚Ä?37 in CRC. Luciferase reporter assay demonstrated the direct interaction between miR‚Ä?37 and 3'‚ÄëUTR of KRAS mRNA. Furthermore, reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that miR‚Ä?37 could negatively regulate endogenous KRAS expression in CRC cells at both mRNA and protein levels. Moreover, KRAS was highly expressed in CRC tissues and inversely correlated with miR‚Ä?37 expression in CRC tissues. KRAS knockdown recapitulates effects similar to those induced by miR‚Ä?37 overexpression in CRC cells, whereas KRAS overexpression partially restored the tumour suppressive effects of miR‚Ä?37. Besides, ectopic expression of miR‚Ä?37 inactivates the AKT and ERK signalling pathways in CRC. These results suggested that miR‚Ä?37 may act as a tumour suppressor during the process of CRC malignant transformation by interacting with KRAS. 

Retracted: No

PubPeer comments:
 Figs 2D and 5D.  The effects of miR-337 overexpression on HCT116 and SW480 cell ... apoptosis were evaluated using ... flow cytometry analysis ;  The effects of KRAS knockdown on HCT116 and SW480 cell ... apoptosis was evaluated with ... flow cytometry analysis .  Figs 3B and 5D from [Shen et al (2018)] .  Downregulation of miR-147 promotes the rate of the 5-FU-induced apoptosis in AGS and BGC-823 cells ;  The rate of 5-FU-induced apoptosis in the indicated cells was evaluated using flow cytometry analysis.  Could the authors comment on the appearance of the red-marked panel within both papers? --------------------------------------- UPDATE: Yellow box added, to mark a matching panel in Figs 2D, 5D, 6D of [Zhao et al (2019)] .  ------------------------------------- UPDATE: light blue boxes added, to match panels in figs 2C,4C,5C of [Jia et al (2018)] .   , 
 Another panel match with Figs 2G,H and 4G,H from [Ji et al (2017)] .  Here in context:  -----------------------------------------  , 
 Retracted [25 August 2022] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that various panels showing data from flow cytometric experiments in Figs. 2D and 5D 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 were already under consideration for publication, or had already been published, elsewhere when it was submitted 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 a reply. The Editor apologizes to the readership for any inconvenience caused. ,