MicroRNA‑130a regulated by HPV18 E6 promotes proliferation and invasion of cervical cancer cells by targeting TIMP2
Authors: Quanle Zhang
Shaoru Li
Yuhong Wang
Shanlan Yin
Ruili Hu
Journal: Experimental and therapeutic medicine (2019)
Discipline: CLINICAL MEDICINE
Keywords: cervical cancer; invasion; microRNA; migration; tissue inhibitor of metalloproteinase 2.
Affiliations: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China

Abstract:  Human papillomaviruses (HPVs) have important roles in the development and progression of cervical cancer, but the underlying mechanisms are yet to be fully elucidated. MicroRNA-130a (miR-130a) has previously been reported to promote cervical cancer growth. However, the underlying molecular mechanisms by which miR-130a promotes cervical cancer progression have remained largely elusive. In the present study, polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR-130a and associated proteins. A wound healing assay and a Transwell assay were applied to study cell migration and invasion. A luciferase reporter gene assay was performed to confirm the targeting associations of miR-130a. It was observed that miR-130a was significantly upregulated in cervical cancer tissues compared with that in adjacent non-tumorous tissues. High expression of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of cervical cancer. Furthermore, the expression of miR-130a was also higher in HPV(+) cervical cancer cell lines compared with that in HPV(-) cells. Knockdown of HPV18 E6 significantly inhibited the expression of miR-130a in HeLa cervical cancer cells. Furthermore, knockdown of miR-130a reduced the migration and invasion of HeLa cells. Tissue inhibitor of metalloproteinase 2 (TIMP2), an antagonist of matrix metalloproteinase 2 (MMP2), was identified as a novel, direct target gene of miR-130a. The expression of TIMP2 was negatively mediated by miR-130a, and HPV18 E6 inhibited the expression of TIMP2 in HeLa cells. Furthermore, knockdown of TIMP2 rescued the suppressive effects of miR-130a downregulation on the migration and invasion of HeLa cells. In summary, the present study suggests that HPV18 E6 promotes the expression of miR-130a, which further inhibits the expression of TIMP2 and promotes cervical cancer cell invasion. Therefore, HPV/miR-130a/TIMP2 signaling may be a potential target for the prevention of cervical cancer metastasis. 

Retracted: Yes

PubPeer comments:
 Figs 2C, 6D. Transwell assays. ![file] Overlaps with Figs 2D, 4E of [Jiang et al (2018)] . Transwell assays. ![file] , 
 Retracted [4 March 2022] .  Following the publication of this paper, it was drawn to the Editorsu2019 attention by a concerned reader that the Transwell cell migration assay data shown in Figs. 2C and 6D 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 had already been published elsewhere, or were already under consideration for publication, prior to its submission to *Experimental and Therapeutic Medicine*, 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 any reply. The Editor apologizes to the readership for any inconvenience caused. ,