Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation
Authors: Yue Wang
Zhe Yang
Yi-Ying Wang
Yong-Jie Li
Journal: Molecular Oncology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: cervical cancer; invasion; metastasis; microRNA-93-3p; paternally expressed gene 3
Affiliations: Department of Obstetrics and Gynecology Henan Provincial People's Hospital People's Hospital of Zhengzhou University Henan University People's Hospital China

Abstract:  Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1), located on human chromosome 19q13.43, is a member of the C2H2 zinc finger protein family. Herein, we aimed to analyze the interactions between ZNF667-AS1, microRNA-93-3p (miR-93-3p), and paternally expressed gene 3 (PEG3) and to explore their roles in the tumorigenesis of cervical cancer (CC). Differentially expressed long noncoding RNAs and miRNAs related to CC were determined using gene expression datasets sourced from the Gene Expression Omnibus database. Subsequently, the regulatory relationships between ZNF667-AS1 and miR-93-3p and between miR-93-3p and PEG3 were identified using the dual-luciferase reporter gene assay. In addition, the expression of miR-93-3p and ZNF667-AS1 was up- or downregulated in CC cells (HeLa), in order to assess their effects on cell cycle distribution and cell invasion in vitro, and tumor growth and metastasis in vivo. MiR-93-3p was found to be highly expressed, while ZNF667-AS1 and PEG3 were poorly expressed in CC. ZNF667-AS1 could competitively bind to miR-93-3p, which targeted PEG3. In addition, miR-93-3p downregulation and ZNF667-AS1 overexpression led to increased expression of PEG3, tissue inhibitor of metalloproteinases, and p16 and decreased expression of cyclin D1, matrix metalloproteinase-2 and -9. MiR-93-3p inhibition and ZNF667-AS1 elevation also inhibited cell cycle entry and cell invasion in vitro, but repressed tumor growth and metastasis in vivo. These key findings demonstrated that upregulation of ZNF667-AS1 could suppress the progression of CC via the modulation of miR-93-3p-dependent PEG3, suggesting a potential therapeutic target for the treatment of CC. 

Retracted: No

PubPeer comments:
 Figs 3C, 3G. ![file] Were these flow-cytometry cell-cycle plots hand-drawn? The G0 G1, S, and G2 M humps vary in shape (not just height) from panel to panel, which doesn t seem right. Each panel contains a wriggly line and a smoother line, where the former (I assume) is supposed to be the raw data and the latter is supposed to sum the G0 G1, S, and G2 M contributions -- except it doesn t. Fig 5I, 5S. The peaks are even wobblier, as if left out in the sun. ![file] , 
  Acknowledgements We would like to thank our researchers for their hard work and reviewers for their valuable advice. I am puzzled. Are the authors thanking themselves? Or are they thanking some other people who **did the research** but do not warrant co-authorship or even acknowledgement by name? , 
 Here is a montage of curious Western Blots I collected, representing a distinct style. They are marked by high contrast and an absence of any background texture, and resemble ink blobs. They are not always sharp-edged; sometimes the ink appears to have spread, creating filaments. When there are double bands (ERK 1 2, JNK 1 2, LC3 I II, the sub-bands are somehow decoupled: differing in overall profile and in the width of the protein blobs, and with horizontal displacements, almost falling into different lanes. The papers that contain them tend to be problematic in other ways (some have been retracted). Their manifestations began in 2019 papers, and stopped in 2020 as if their use became deprecated. ![] Sources include - [He et al (2020)] - [Chang et al (2020)] - [Shang et al (2020)] - [Shi et al (2019)] *[RETRACTED]* - [Xu et al (2019)] *[RETRACTED]* - [Jia et al (2020)] - [Feng et al (2019)] Examples could be multiplied but I will settle for three more examples, to show the range of this gamut, from - [Qu et al (2019)] *[RETRACTED]* - [Song et al (2019)] *[RETRACTED]* - [Shi et al (2019)] . ![file] ---------------------------------------------- Here are the present Figs 5B, L, G, Q;  The protein bands of MMP-2, MMP-9, PEG3, and TIMP-2 in western blot analysis after the cells were transfected with pcDNAZNF667-AS1 and si-ZNF667-AS1 ... The protein bands of cyclin D1, PEG3, and p16 in western blot analysis after the cells were transfected with pcDNA-ZNF667-AS1 and si-ZNF667-AS1 . They appear to be manifestations of the same style. Is it possible for the authors to upload or link to scans of the original blots, to allay any concerns? ![file] ,