MicroRNA-92a promotes tumor growth and suppresses immune function through activation of MAPK/ERK signaling pathway by inhibiting PTEN in mice bearing U14 cervical cancer
Authors: Lei Li
Lin-Ping Kang
Zeng-Hui Li
Yan Wang
Journal: Cancer Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: PTEN; Immune function; MAPK/ERK signaling pathway; MicroRNA-92a; U14 cervical cancer.
Affiliations: Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China., Department of Obstetrics and Gynecology, Qingdao Municipal Hospital, Qingdao, 266071, China., Department of Obstetrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, P.R., China.

Abstract:  Cervical cancer is known as the possible outcome of genital infection, while the molecular mechanisms of initiation, development, and metastasis of cervical cancer have not yet been fully elucidated. Our study aims to investigate the effects of microRNA-92a (miR-92a) on tumor growth and immune function by targeting PTEN via the MAPK/ERK signaling pathway in tumor-bearing mice. C57BL/6 female mice were used for tumor-bearing mouse models and their tumor and adjacent normal tissues were collected, and normal cervical tissues were obtained from normal mice. Serum levels of tumor necrosis factor-Œ± (TNF-Œ±) and soluble interleukin-2 receptor (sIL-2R) were detected by ELISA. The cells were divided into the normal, blank, negative control (NC), miR-92a mimic, miR-92a inhibitor, siRNA-PTEN, and miR-92a inhibitor + siRNA-PTEN groups. Dual-luciferase reporter assay was adopted to determine the relationship between PTEN and miR-92a. Expressions of miR-92a, PTEN, TNF-Œ±, sIL-2R, ERK1, and ERK2 were tested by RT-qPCR and Western blotting. Cell proliferation was detected by cell count kit-8 (CCK-8); cell cycle and apoptosis were detected by flow cytometry. Compared with the normal cervical tissues and adjacent normal tissues, the cervical cancer tissues exhibited increased expressions of miR-92a, p-ERK1/2, and serum levels of TNF-Œ± and sIL-2R while decreased PTEN expression. PTEN was confirmed to be the target gene of miR-92a. As compared with the blank and NC groups, expressions of miR-92a, ERK1 and ERK2 increased, and expressions of PTEN decreased in the miR-92a mimic group. The miR-92a mimic group exhibited increased expression levels of TNF-Œ± and sIL-2R, cell proliferation, and cell number in S phase but decreased cell apoptosis, and cell number in G0/G1 phase, while the miR-92a inhibitor group followed opposite trends. miR-92a promotes tumor growth and suppresses immune function by inhibiting PTEN via activation of the MAPK/ERK signaling pathway in mice bearing U14 cervical cancer. 

Retracted: Yes

PubPeer comments:
 Fig 6A.  Cell apoptosis in seven groups after transfection. (A) cell apoptosis in seven groups . I have concerns.  , 
 Fig 7A.  Changes in cell cycle distribution in seven groups after transfection. (A) cell cycle under microscope . It is not clear to me where the microscopy is involved in flow cytometry. Nor is it clear how these alarming overhangs developed in the raw data.  , 
 Fig 4B.  MiRu201092a expression and mRNA and protein expression of PTEN, TNFu2010u03b1, sILu20102R and ERK1 2 in seven groups after transfection. A, miRu201092a expression, mRNA expression of PTEN, TNFu2010u03b1, sILu20102R and ERK1 2; B, Western blotting map *[sic]* .  The protein blobs seem to come from the same restricted gamut shown in this montage.  , 
 #3 *[left]* Fig 4B again. *[right]* Fig 7b from [Shao Xia (2019)] .  western blot analysis was used to determine the relative protein expressions of BDNF and Sox2 .  Could the authors of either paper comment on the appearance of the same loading control in these otherwise-unrelated studies? , 
 Retracted [27 September 2021] . ------------------------- The above article, published online on May 11, 2018 in Wiley Online Library has been retracted by agreement between the the journalu2019s Editor in Chief and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data (figures 2B and 4B) were published elsewhere in a different scientific context. Furthermore, several methodical flaws and inconsistencies were found. Thus, the editor considers the conclusions of this article to be invalid.u202fThe authors were not available to comment on these inconsistencies. ,