Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer
Authors: Fei Liang
Jian Zhao
Fuli Zhao
Ying Guo
Journal: Molecular and cellular biochemistry (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Breast cancer; HK2; Proliferation; Resibufogenin; Warburg effect
Affiliations: Department of Breast and Thyroid Surgery, Provincial Hospital Affiliated To Shandong University, Jingwu Road 324, Huaiyin District, Jinan, 250021, Shandong, China., Department of Breast and Thyroid Surgery, Provincial Hospital Affiliated To Shandong University, Jingwu Road 324, Huaiyin District, Jinan, 250021, Shandong, China. .

Abstract:  Increasing evidence confirmed that the Warburg effect plays an important role involved in the progression of malignant tumors. Resibufogenin (RES) has been proved to have a therapeutic effect in multiple malignant tumors. However, the mechanism of whether RES exerted an antitumor effect on breast cancer through regulating the Warburg effect is largely unknown. The effect of RES on glycolysis was determined by glucose consumption, lactate production, ATP generation, extracellular acidification rate and oxygen consumption rate in breast cancer cells. The total RNA and protein levels were respectively measured by RT-qPCR and western blot. Cell proliferation and apoptosis were examined using the CCK-8 assay, colony formation assay, and flow cytometry, respectively. The interaction between miR-143-3p and HK2 was verified by dual-luciferase reporter gene assay. We also evaluated the influence of RES on the tumor growth and Warburg effect in vivo. RES treatment significantly decreased glycolysis, cell proliferation and induced apoptosis of both MDA-MB-453 and MCF-7 cells. Simultaneously, the expression of HK2 was decreased in breast cancer cells treated with RES, which was positively associated with tumor size and glycolysis. Moreover, HK2 was a direct target gene of miR-143-3p. Mechanistically, upregulation of miR-143-3p by RES treatment inhibited tumor growth by downregulating HK2-mediated Warburg effect in breast cancer. Our findings suggested that RES exerted anti-tumorigenesis and anti-glycolysis activities in breast cancer through upregulating the inhibitory effect of miR-143-3p on HK2 expression, which provided a new potential strategy for breast cancer clinical treatment. 

Retracted: No

PubPeer comments:
 Fig 2D,  Flow cytometry was performed to evaluate the cell apoptosis .  Cf. 3B from [Liu Yu (2018)] :  Also [Dou et al (2019)] , and [below] 2A from [Wang et al (2018)] .  , 
 Fig 6D.  Colony formation assay was applied to detect the cell proliferation ability in both MDA-MB-453 and MCF-7.   For comparison, Fig 1B from [Jin et al (2017)] ,  Icaritin suppresses OSCC cell growth in dose- and time-dependent manner. .... B. Icaritin inhibits cell proliferation . Many other manifestations in that thread.  For more details I refer readers to a Google spreadsheet: https: docs.google.com spreadsheets d 13K6zoo2oSATsFlY7YGyvm2_Xs1jibs0RH4nKQP5y8DY edit#gid=0 and a blogpost. https: forbetterscience.com 2020 02 27 dark-satanic-papermills , 
 Fig 7F.  Fig 3D from [Deng et al (2020)] . More manifestations in that thread.  , 
 #2 Then there s this:  Fig 6D, recolored for comparison with Fig 1D of [Liu et al (2018)] .  , 
 http: www.most.gov.cn zxgz kycxjs kycxgzdt 202201 t20220127_179206.html Google Translated Date: January 27, 2022 14:44 Source: Ministry of Science and Technology u3000u300035. The paper  Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p HK2 axis in breast cancer of Shandong First Medical University with Guo Ying as the first author and Zhao Jian as the corresponding author. After investigation, it was found that the paper was tampering with data, writing and investing on behalf of others. Zhao Jian will be dealt with as follows: scientific research integrity admonition talk; Guo Ying will be dealt with as follows: scientific research integrity admonition talk, cancel the qualification to participate in the current year s first-class evaluation, the annual evaluation cannot be determined as excellent, and cancel the application or application for science and technology plan projects Eligibility for 3 years, cancellation of qualifications as nominees or recommenders, nominated or recommenders, review experts, etc. for 3 years. u3000u3000(Notification link: https: sr.sdfmu.edu.cn info 1011 1967.htm) , 
 Retracted [13 September 2022] . ------------------- The Editors-in-Chief have retracted this article because of significant concerns regarding a number of Figures presented in this work, which question the integrity of the data. Specifically: - Figure 2D contains images that appear to be the same or nearly the same as those published previously in a number of unrelated publications, such as Fig. 3B in [1] (now retracted), - Figure 6D contains images that appear to be the same or nearly the same as those published previously in a number of unrelated publications, such as Fig. 1D in [2] and Fig. 1B in [3] - Figure 7F contains images that appear to be the same as those published previously in Fig. 3D in [4] The Chinese Ministry of Science and Technology conducted an investigation which found the data presented here has been tampered with. The Editor-in-Chief therefore no longer have confidence in the integrity of the data in this article. None of the authors have responded to any correspondence from the editor or publisher about this retraction. **References** - [1] RETRACTED: Liu B, Yu S (2018) Amentoflavone suppresses hepatocellular carcinoma by repressing hexokinase 2 expression through inhibiting JAK2 STAT3 signaling. Biomed Pharmacother 107:243u2013253. https: doi.org 10.1016 j.biopha.2018.07.177 - [2] Liu L et al (2018) Resibufogenin suppresses transforming growth factor-u00df-activated kinase 1-mediated nuclear factor-u03baB activity through protein kinase C-dependent inhibition of glycogen synthase kinase 3. Cancer Sci 109(11):3611u20132622. https: doi.org 10.1111 cas.13788 - [3] Jin L, Miao J et al (2017) Icaritin induces mitochondrial apoptosis by up-regulating miR-124 in human oral squamous cell carcinoma cell. Biomed Pharmacother 85:287u2013295. https: doi.org 10.1016 j.biopha.2016.11.023 - [4] Deng M et al (2020) Chrysophanol exhibits inhibitory activities against colorectal cancer by targeting decorin. Cell Biochem Funct 38(1):47u201357. https: doi.org 10.1002 cbf.3445 ,