MicroRNA-487a promotes proliferation of esophageal cancer cells by inhibiting p62 expression
Authors: Y Wang
J-B Ma
R-K Zang
Y Su
Y-C Liang
S-L Hu
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MicroRNA-487a; esophageal cancer; oncogene; biological role; mechanism
Affiliations: Department of Radiotherapy, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. .

Abstract:  Objective: MicroRNAs are endogenous, non-coding, small RNAs that can regulate biological processes. Previous studies have found that microRNA-487a serves as an oncogene. However, the role of microRNA-487a in esophageal cancer (EC) has not been reported. The aim of this investigation was to investigate the biological role of microRNA-487a in EC and its underlying mechanism. Patients and methods: The expression of microRNA-487a in 65 pairs of EC tissues and para-cancerous tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-487a expression with age, sex, clinical stage and distant metastasis of OS patients. Kaplan-Meier survival analysis was conducted to evaluate the correlation between microRNA-487a expression and prognosis of EC patients. Subsequently, microRNA-487a expression in EC cell lines was detected as well. After microRNA-487a knockdown, cell counting kit-8 (CCK-8), EdU and transwell assay were conducted to evaluate the role of microRNA-487a in the biological performances of EC cells, respectively. Meanwhile, the apoptosis of EC cells was determined using flow cytometry. Finally, the interaction between microRNA-487a and p62 was explored by Western blot. Transwell assay was carried out in EC cells co-transfected with p62 overexpression plasmid and si-microRNA-487a. Results: Compared with para-cancerous tissues, microRNA-487a expression was significantly higher in EC tissues, and the difference was statistically significant. MicroRNA-487a was highly expressed in EC cells as well. Low expression of microRNA-487a was positively correlated with clinical stage, whereas was not correlated with age, sex, lymph node metastasis and distant metastasis of EC patients. Kaplan-Meier survival curves showed that high expression of microRNA-487a was markedly associated with poor prognosis of EC. The knockdown of microRNA-487a significantly inhibited proliferative, migratory and invasive abilities of EC cells but induced cell apoptosis. Western blot results showed that the protein expression of p62 was remarkably upregulated after microRNA-478a knockdown in EC cells. Transwell assay demonstrated that co-transfection with overexpression plasmid of p62 and si-microRNA-487a in EC cells markedly decreased invasive and migratory abilities. Conclusions: MicroRNA-487a is highly expressed in EC and is closely correlated with clinical stage and poor prognosis of EC. Our findings confirm that microRNA-487a promotes malignant progression of EC by regulating p62 expression. 

Retracted: No

PubPeer comments:
 This paper is part of a group of papers with a characteristic Kaplan Meier curve with a comb-like appearance. These plots all have a drop to 0 % survival at 75 months, a.k.a  Hoya s Law . Within the Comb papers, there is a subgroup of at least 9 papers that have very similar negative correlation plots. * X Shi et al., ERMPS (2019), DOI: 10.26355 eurrev_201912_19778 - https: pubpeer.com publications 3133C4267A6FBF81D00B0AF9FB9F2C * CY Yang et al., ERMPS (2019), DOI: 10.26355 eurrev_201908_18736 - https: pubpeer.com publications 04A58FD5AFBB311D1A2938B0612E1E * HG Zhang et al., ERMPS (2019), DOI: 10.26355 eurrev_201903_17239 - https: pubpeer.com publications D916E15502393940A4F3151E1D300C * JY Chen et al, ERMPS (2020), DOI: 10.26355 eurrev_202001_20040 - https: pubpeer.com publications 9266A736E004B8D7C32F6811161C1C * SS Li et al., ERMPS (2020) - DOI: 10.26355 eurrev_202002_20163 - https: pubpeer.com publications 5CDE9845135F510EC218243CD501F9 * TZ Zheng et al., ERMPS (2020) - DOI: 10.26355 eurrev_202002_20369 - https: pubpeer.com publications AF0159381E48D7937D78C948FAB379 * JB Ma et al., ERMPS (2019) - DOI: 10.26355 eurrev_201902_17108 - https: pubpeer.com publications 2EB1B6A17E9877F2D7F8FE4E117446 * HW Sun et al., ERMPS (2019)- DOI: 10.26355 eurrev_201910_19299 - https: pubpeer.com publications 937B0CAD1A01B66E854F4A6CCDA56B * K Jia et al., ERMPS (2020) - DOI: 10.26355 eurrev_202003_20508 - https: pubpeer.com publications 11550517E8A0503AFDC49D460BAD30 And here is a collage of the nine correlation plots, where I have circled some similar groupings of points. ![file] , 
 *[left]* Fig 1D from [Ma et al (2019)] .  Survival curves of microRNA-487a expression in EC patients. *[right]* Fig 1D from [Zang et al (2018)] .  Kaplan-Meier survival curves of patients with esophageal cancer based on microRNA-124 expression. Patients in the high expression group had worse prognosis than those in the low expression group. ![file] My goal here is to call attention to the unexpected similarities, especially in the two lower curves. ,