CircRNA_100876 promote proliferation and metastasis of breast cancer cells through adsorbing microRNA-361-3p in a sponge form
Authors: S-Q Wang
J-N He
C-Y Yang
F-X Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: circRNA_100876; breast cancer; metastasis; microRNA-361-3p; prognosis
Affiliations: Queen Mary School, Nanchang University, Nanchang, China. .

Abstract:  Objective: This study was designed to investigate the expression level of circRNA_100876 in breast cancer (BC) tissues or cells, and to further explore whether it can promote cell metastasis and proliferative capacity via targeting microRNA- 361-3 p. Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of circRNA_100876 in 50 pairs of BC tissue specimens and corresponding adjacent ones, and the correlation between circRNA_100876 expression and prognosis of patients with BC was analyzed. Meanwhile, qRT-PCR was further performed to verify circRNA_100876 level in BC cell lines. In addition, circRNA_100876 knockdown model was constructed using lentivirus and transfected in BC cells. Subsequently, the impact of circRNA_100876 on BC cell function was analyzed using Cell Counting Kit-8 (CCK-8), transwell and clone formation assays. The interplay between circRNA_100876 and microRNA- 361-3 p was verified using the Luciferase reporter gene assay and cell reverse experiment. Results: QRT-PCR results showed that circRNA_100876 level in BC tissues was conspicuously higher than that in the adjacent tissues, and the patients with distant metastasis had higher expression than those without. Moreover, patients with a high expression of circRNA_100876 had a relatively lower overall survival rate. Compared with the NC group, the cell proliferation and invasion ability of circRNA_100876 knockdown group was conspicuously decreased. QRT-PCR revealed that microRNA-361-3p and circRNA_100876 showed a negative correlation in the expression level of genes in BC tissues. In addition, the results of the Luciferase reporter gene assay confirmed that circRNA_100876 can be targeted by microRNA-361-3p through their binding site. Conclusions: High expression of circRNA_100876 is conspicuously positively relevant to poor prognosis of BC patients. Additionally, circRNA_100876 is able to promote BC metastasis as well as proliferative capacity by modulating microRNA-361-3p expression. 

Retracted: No

PubPeer comments:
 Figs 1D, 3E.  The Kaplan-Meier survival curve of breast cancer patients based on circRNA_100876 expression showed that patients with high expression group had significantly worse prognosis than low expression group ...  The Kaplan-Meier survival curve of breast cancer patients based on miR-361-3p expression indicated that the prognosis of patients with low expression was significantly worse than that of the high expression group . ![file] It is not possible to obtain these two pairs of survival curves from the same group of 50 BC cases, dichotomised by two different criteria. Deaths in one pair cannot be matched to deaths in the other. Notably, at the 75-month end-point, both groups in 1D have lower survival than their counterparts in 3E. This is a recurring problem in this oeuvre. See, for instance, Figs 1C, 3D from [Zheng et al (2019)] . ![] , 
 *[left]* Fig 3D from [Yang et al (2019)] .  There was a significant negative correlation between the expression levels of circRNA_100876 and miR-361-3p in breast cancer tissues . *[right]* Fig 1E from [Shi et al (2019)] .  Negative correlation between expression levels of miR-188-5p and PAPAS. More shared points than one would expect. ![file] , 
 Extended to a three-way superimposed comparison, introducing *[lower left]* Fig 3D from [Zhang et al (2019)] .  Negative correlation between expressions of TRIM66 and E-cadherin in HCC tissues both at mRNA and protein levels . ![file] , 
 Some other papers also have similar correlation plots, bringing the total now to 9. These papers also all have the  comb-like survival plots following  Hoya s Law , with a sudden drop at 75 months. I have been calling this the  Comb group of papers. Here is a list of the papers identified so far that all have this particular negative correlation plot. * 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] ,