MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway
Authors: Yong-Jian Wang
Xin Wen
Bin Hu
Chun-Hui Sun
Jun Lu
Shan Wang
Shao-Hua Fan
Qun Shan
Yuan-Lin Zheng
Dong-Mei Wu
Xin-Rui Han
Juan Zhuang
Min Shen
Xiao-Wu Hong
Meng-Qiu Li
Zi-Feng Zhang
Journal: IUBMB life (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MCL1; PI3K/Akt signaling pathway; apoptosis; gene silencing; glioma
Affiliations: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, China., College of Health Sciences, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China., Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, 221008, China., Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, School of Life Sciences, Huaiyin Normal University, Huaian, 223300, China.

Abstract:  Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit-8 assay was applied to detect cell proliferation, β-galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81-92, 2019. 

Retracted: No

PubPeer comments:
  Flow cytometry analysis of Annexinu2010V PI double staining shows that silencing of MCL1 promotes glioma cell apoptosis. (A) Flow cytometry map demonstrating glioma cell apoptosis conditions . The NC and Blank panels are superficially different, but this is limited to the peripheral stippling -- the continents of cells in the lower left quadrants are internally the same. ![file] ![file] By looking at a smaller area of internal structure, one can extend the overlap to include the IGF-1 panel. ![file] , 
 Assessed here, as part of the first of 10 broad investigations: https: www.nsfc.gov.cn publish portal0 tab442 info85495.htm **Decisions on handling scientific research misconduct cases investigated and dealt with in 2022 (first batch)** Date 2022-05-13 Source: u3000 Author: u3000 u3010 Large, Middle and Small u3011 u3010Printu3011 u3010Closeu3011 u3000u3000The National Natural Science Foundation of China resolutely implements the spirit of the  Several Opinions on Further Strengthening the Construction of Scientific Research Integrity and  Opinions on Further Promoting the Spirit of Scientists and Strengthening the Construction of Style and Study Style by the General Office of the Central Committee of the Communist Party of China and the General Office of the State Council. Horizontal science and technology are self-reliant and self-reliant, continue to carry out scientific research integrity construction, and seriously investigate and deal with scientific research misconduct involving the National Natural Science Foundation of China. The Supervision Committee of the National Natural Science Foundation of China conducts investigations, verifications and comprehensive judgments on the accepted scientific research integrity cases, in accordance with the Regulations of the National Natural Science Foundation of ) and  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China and other regulations and systems to propose handling suggestions. After deliberation at the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to deal with the relevant parties involved. The 10 handling decisions (online release version) that have been criticized and criticized are hereby announced. -------------------------------- About the existence of papers published on Wu Dongmei, Zheng Yuanlin, Lu Jun, etc. - Falsification of pictures or data, fabrication of research process, use of others signatures without consent, and false information in project final reports - processing decision - National Science and Technology Financial Supervisory Office [2022] No. 1 u3000u3000The Supervision Committee of the National Natural Science Foundation of China launched an investigation into several papers of Jiangsu Normal University, including Wu Dongmei, Zheng Yuanlin, and Jun Jun, for suspected academic misconduct. The papers involved are as follows: ... Paper 35:  Dong-Mei Wu, Xiao-Wu Hong, Xin Wen, Xin-Rui Han, Shan Wang, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng -Qiu Li, Bin Hu, Chun-Hui Sun, Jun Lu*, Yuan-Lin Zheng*. **MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K Akt signaling pathway**. IUBMB Life, 2019, 71(1 ): 81-92.u201d (marked with fund numbers 81271225, 31201039, 81171012, 30950031, 81571055, 81400902) u3000u3000According to the investigation of the supporting unit, the above 35 papers involved all have the problem of improper use of pictures or data fraud, and the pictures or data in question are all provided by third-party companies. Among the 35 papers involved, 34 (except paper 21) still have the problem of using others signatures without consent, and papers 4, 5, 9, 12, 30, and 34 also have the problem of fabricating the research process. Wu Dongmei is the author of the above 35 papers involved, of which 12 papers (papers 2, 8, 9, 10, 11, 12, 14, 15, 25, 26, 30, 35) are the first author and 22 papers (Paper 1, 4, 5, 6, 7, 13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 27, 28, 29, 31, 32, 33, 34) Corresponding author, They should be primarily responsible for the objective results of falsifying pictures or data, using others signatures without consent, and fabricating research processes; Zheng Yuanlin and Lu Jun, as the co-corresponding authors of the 35 papers involved, were negligent in reviewing and took secondary responsibility. In addition, Wu Dongmei included 4 papers involved (papers 21, 24, 28, 29) in the final report of the National Natural Science Foundation of China (Grant No. 81400902), and Zheng Yuanlin included 9 papers involved (papers 6, 8, 10, 13, 21, 24, 26, 28, 29) included in the final report of the National Natural Science Foundation of China (Grant No. 81571055), and should be responsible for the objective results of false information in the final report. u3000u3000After deliberation at the 12th meeting of the Fifth Supervision Committee of the National Natural Science Foundation of China (Life Medicine Professional Committee) and the approval of the second executive meeting of the National Natural Science Foundation of China in 2022, it was decided to follow the thirty-fifth National Natural Science Foundation of China Regulations. Article 4, Article 17, Items 3, 4, and 9 of  Measures for Handling Misconduct in Science Fund Work by the Supervision Committee of the National Natural Science Foundation of China (for Trial Implementation) , revocation of Wu Dongmei s National Natural Science Foundation of Molecular mechanism of TRPV4-mediated domoic acid treatment-induced cognitive deficits in mice (Grant No. 81400902), recovering the allocated funds, permanently disqualifying Wu Dongmei from the National Natural Science Foundation of China (since January 18, 2022), Give Wu Dongmei a circular of criticism; decide to follow Article 35, item 4 of the  National Natural Science Foundation of China Regulations , and refer to  The National Natural Science Foundation of China Supervision Committee s Handling of Misconduct in Science Fund Work (Trial) Tenth Items 3 and 4 of seven articles, the Zheng Yuanlin National Natural Science Foundation of China project  The Mechanism of HDAC6 Activating HMGB1 RAGE Signaling Axis to Mediate Cognitive Defects in Type 2 Diabetic Mice (Approval No. 81571055), recover the allocated funds, cancel Zheng Yuanlin will be eligible to apply for the National Natural Science Foundation of China for 5 years (January 18, 2022 to January 17, 2027), and will give Zheng Yuanlin a notice of criticism; it is decided to refer to the  National Natural Science Foundation of China Supervision Committee on misconduct in the work of the National Natural Science Foundation of China. Items 3 and 4 of Article 17 of the Measures (for Trial Implementation), the Army s National Natural Science Foundation of China project application qualification will be cancelled for 5 years (January 18, 2022 to January 17, 2027), and the Army will be criticized in a circular. - National Natural Science Foundation of China - March 30, 2022 , 
 Retracted [10 October 2022] .  The above article, published online on October 8, 2018 in Wiley Online Library, has been retracted by agreement between the Editor-in-Chief (Stathis Gonos), the International Union of Biochemistry and Molecular Biology, and Wiley Periodicals LLC. The retraction was agreed on concerns raised by a third party, which were followed by an investigation of the Academic Committee of Jiangsu Normal University in collaboration with independent referees. During this investigation, authors failed to provide original experimental records and data. The investigation concluded that the academic integrity of this manuscript is violated. ,