miR-133a inhibits cervical cancer growth by targeting EGFR
Authors: Bo Shi
Kexin Huang
Wenjie Zhang
Xuesong Song
Journal: Oncology Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-133a; cervical cancer; tumorigenicity; metastasis
Affiliations: Department of Anesthesiology, The First Hospital of Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China., The Experiment Center, College of Basic Medical Sciences, Jilin University, Chaoyang, Changchun, Jilin 130021, P.R. China., Department of Pathology, China‑Japan Union Hospital of Jilin University, Nanguan, Changchun, Jilin 130033, P.R. China.

Abstract:  MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in cervical carcinogenesis and progression. microRNA-133a (miR-133a) has been reported to play a tumor-suppressor role in a range of cancers. However, the role and underlying molecular mechanism of miR-133a in cervical cancer have not been investigated. In the present study, we investigated the role of miR-133a in the tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-133a was investigated using real-time reverse transcription-polymerase chain reaction (qRT-PCR) in 30 cervical specimens and matched adjacent normal tissues and cervical cancer cell lines. We found that the expression level of miR‑133a was significantly downregulated in cervical cancer tissues and cervical cancer cell lines, and the aberrant expression of miR-133a was correlated with lymph node metastasis, histological grade and FIGO stage. The role of miR-133a in tumorigenicity of cervical cancer cells was assessed by the restoration of miR-133a. We found that restoration of miR‑133a inhibited cell proliferation, colony formation, migration and invasion, promoted cell apoptosis in vitro and suppressed tumorigenicity in vivo. The epidermal growth factor receptor (EGFR) was confirmed to be a direct target of miR-133a in cervical cancer cells using luciferase assay and western blotting. Restoration of miR-133a inhibited EGFR expression and activated the AKT and ERK signaling pathways. These results showed that miR-133a suppresses cervical cancer growth in vitro and in vivo through targeting EGFR, suggesting that miR-133a can be a potential target for the treatment of cervical cancer. 

Retracted: Yes

PubPeer comments:
 *[left]* Fig 5C.  Western blotting of EGFR protein expression in the HeLa cells after transfection with the miR-133a mimic or miR-Ctrl. u03b2-actin was used as an internal control. *[right]* Fig 3c from [Zhang et al (2015)] .  The expression levels of MMP-2 and MMP-9 were determined by Western blot after being transfected with miR-133a or miR-NC. GAPDH was used as internal control . ![file] Unexpected similarity. ------------------------------ UPDATE. A few more colored rectangles added, to highlight similarities to Fig 6 of [Liu et al (2015)] . ![file] , 
 Dear editor, Thank you for your comments. Our team will investigate these questions and get back to you soon. Thank you for your work. Best regards , 
 Another appearance here: Fig 5D from [Wang et al (2016)](http: www.ijcem.com files ijcem0017368.pdf),  IRS2 protein expression was determined in four ovarian cancer cell lines (SKOV3, A2780, OVCAR and HO-8910) and human ovarian surface epithelial cell line (HOSEpiC) . ![] The journal in that case, IJCEM, is not Pubmed accredited, and did not bother with DOIs, so it isn t possible to start a separate PubPeer thread for it. UPDATE: Another sighting! Figs 1C, 4C from [Zhang et al (2015)] . ![] , 
 Fig 3E.  Determination of the capacity for colony formation of HeLa cells using a colony formation assay after transfection with miR-133a or miR-Ctrl . ![file] Fig 2C from [Zhao et al (2015)] .  Effects of miR-491-5p overexpression on the colony formation of cervical cancer cells were determined . ![] , 
 #1 *[upper right]* Fig 5C again. *[lower right]* Fig 3C from [Zhang et al (2015)] .  The expression levels of MMP-2 and MMP-9 were determined by Western blot after being transfected with miR-133a or miR-NC . *[left]* Fig 1B from [Zhang et al (2018)] .  CREB1 protein expression level was measured in mGCs by western blot 48 h after transduction . ![file] , 
 *[left]* Fig 2A from [Liu et al (2015)] .  Effect of DOX and Ad sh-NOB1 alone or in combination on cell cycle of TPC-1 cells. (A) Cell DNA content distribution in each phase . *[upper right]* Fig 2C from [**Song et al (2015)**] .  Determination of HeLa cell cycle distribution by PI staining after transfection with miR-133a or miR-Ctrl . *[lower right]* Fig 2d from [Zhang et al (2015)] .  The cell cycle was detected by PI staining after being transfected with miR-133a or miR-NC. ![file] The same panels keep appearing. --------------------------------------------------- Clockwise from top left: - Fig 3A from [Liu et al (2015)] .  Effects of miR-222 inhibitor on HepG2 cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015)] .  Effects of microRNA-145 (miR-145) on multiple myeloma (MM) cell cycle distribution. (A) Cell DNA content distribution in each phase. - Fig 3A from [Li et al (2015)] .  Enforced expression of miR-338-3p induced cell cycle distribution and cell apoptosis in EC9706 cells. (A) Cell DNA content distribution in each phase. - Fig 3A from [Zhang et al (2015b)] ,  miR-137 induces changes in cell cycle distribution and cell apoptosis in SKOV3 cells. (A) Cell DNA content distribution in each phase ![file] The same panels keep appearing. ----------------------------------------------------- Clockwise from upper left: - Fig 2D from [Pang et al (2015)] .  cell cycle progression ... determined in HepG2 cells transfected with the miR-154 mimic or miR-NC. - Fig 2D from [Zhao et al (2017)] .  cell cycle stage ... assessed in MM1S cells transfected with miR-144-3p mimic or miR-NC. - Fig 2D from [Li et al (2016)] .  The cell cycle procession was detected by flow cytometry after transfection with miR-494 or miR-NC . - Fig 2C from [Luan et al (2015)] .  Cell cycle was measured in glioma cells at posttransfection by flow cytometry . ![file] The same panels keep appearing. --------------------------------- Fig 2D from [Zhou et al (2016)] .  Cell cycle distribution of U2OS cells transfected with the miR-154 mimic was determined by flow cytometry . ![file] , 
 Retracted [2 June 2021] .  Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that the western blotting data in Fig. 5c were strikingly similar to data appearing in different form in other articles by different authors at different research institutes. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. ,