MicroRNA‚Ä?95 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation√Ø¬ø¬Ω1 domain containing 1 in cervical cancer
Authors: Hui Yuan
Xiangqian Xu
Shoufang Kong
Jinyan Zhong
Journal: International Journal of Molecular Medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: MicroRNAs; miR-195; cervical cancer; DCUN1D1; metastasis
Affiliations: Department of Gynecology, Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.

Abstract:  MicroRNAs (miRs), a class of small non‚Äëcoding RNAs, have been demonstrated to perform promoting or suppressive roles in various types of human malignancy. Deregulation of miR‚Ä?95 has been observed in numerous types of human cancer, including cervical cancer; however, the detailed molecular mechanism of miR‚Ä?95 underlying the malignant progression of cervical cancer remains largely unclear. In the present study, miR‚Ä?95 was significantly downregulated in cervical cancer tissue samples compared with adjacent non‚Äëtumor tissue samples, and the reduced expression level of miR‚Ä?95 was associated with node metastasis and an advanced clinical stage in cervical cancer. Furthermore, the patients with low miR‚Ä?95 expression levels demonstrated shorter survival times when compared with those with high miR‚Ä?95 expression levels. In vitro experiments indicated that miR‚Ä?95 exerted suppressive effects on the proliferation, migration and invasion of cervical cancer cells. Luciferase reporter gene assay identified defective in cullin neddylation 1 domain containing 1 (DCUN1D1) as a novel target gene of miR‚Ä?95 and the expression level of DCUN1D1 was identified to be negatively regulated by miR‚Ä?95 in cervical cancer cells. DCUN1D1 was significantly upregulated in cervical cancer, with a negative correlation to miR‚Ä?95 expression. Furthermore, upregulation of DCUN1D1 was associated with the malignant progression and poor prognosis of cervical cancer. DCUN1D1 overexpression attenuated the suppressive effects of miR‚Ä?95 on the malignant phenotypes of cervical cancer cells. Notably, the expression levels of miR‚Ä?95 were significantly lower in HeLa [human papilloma virus (HPV)18+] and SiHa (HPV16+) cells compared with those in C33A (HPV‚Ä? cells, and knockdown of E6 using small interfering RNA significantly increased the miR‚Ä?95 expression while the DCUN1D1 expression level was reduced in HeLa and SiHa cells. Thus, these findings indicate that miR‚Ä?95 exerts a suppressive role in cervical cancer by targeting DCUN1D1. Therefore, miR‚Ä?95 may present as a potential therapeutic candidate for cervical cancer. 

Retracted: Yes

PubPeer comments:
 Figs 3b, 7b. Transwell assays. Bright green rectangles mark overlap between two panels (after a 180-deg flip).  Coloured rectangles also mark details from Figs 2D, 4C of [Ma et al (2017)] .  Transwell assays were used to determine cell ... invasion capabilities .  Also Fig 4A of [Lei et al (2014)] ,  and Fig 5A of [Long et al (2016)] .  , 
 Fig 7A. Wound-healing assays. 0-Hour Panels for HeLa and SiHa panels seem to be the same (bright green rectangles).  More concerning are the overlaps with Fig 6C (Wound healing assay) of [Xia et al (2018)] . Marked with orange, violet. The two 0-hour panels of 6C are repeated with a 180-deg flip.  Also overlaps with U251 panels of Fig 4D of [Jiang et al (2018)] .  , 
 #1 Figs 3B, 7B. Improved.  Another comparison with Figs 3B and 7B of [Xiao et al (2018)] .  , 
 Retracted [31 May 2021] . -------------------------------------------------- Following the publication of this paper, it was drawn to the Editors attention by a concerned reader that certain of the Transwell assay data in the article (featured in Figs. 3B and 7B) were strikingly similar to data appearing in different form in other articles by different authors at different research institutes that had already been published elsewhere at the time of the present article s submission. Furthermore, the scratch wound assay data in Fig. 7A of the above paper were strikingly similar to data published elsewhere. Owing to the fact that the contentious data in the above article had already appeared in different form in other articles prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors did not reply to indicate whether or not they agreed with the retraction of the paper. The Editor apologizes to the readership for any inconvenience caused. ,