Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway
Authors: Xiaobao Gong
Kai Yang
Huan Liu
Journal: Journal of Cancer (2020)
Discipline: CLINICAL MEDICINE
Keywords: Period 2; autophagy; carcinogenesis; clock genes; oral cancer.
Affiliations: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, People's Republic of China.

Abstract:  The current studies reveal that the clock gene Per2 is expressed at lower levels in a variety of tumors and plays a significant tumor suppressor role. However, the biological functions and mechanism of Per2 in OSCC (OSCC: oral squamous cell carcinoma) remain unclear. In this study, OSCC cells with stable overexpression or silencing of Per2 were established to explore their biological functions and mechanism in vivo and in vitro. We discovered that the expression of Per2 decreases in OSCC cells. Overexpression of Per2 promoted autophagy and apoptosis in OSCC cells and inhibited proliferation. The opposite results were obtained in Per2-silenced OSCC cells. In Per2-overexpressing OSCC cells, the expression levels of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were significantly reduced and the LC3B II/I ratio was significantly increased. In contrast, in Per2-silenced OSCC cells, the expression levels of PIK3CA, p-AKT, p-mTOR, p62 and Beclin1 were significantly enhanced and the LC3B II/I ratio was significantly reduced. When the AKT activator SC79 was added to Per2-overexpressing OSCC cells, the increased autophagy, apoptosis and decreased proliferation were significantly rescued. Furthermore, when autophinib, an autophagy inhibitor, was added to Per2-overexpressing OSCC cells, the decreased proliferation and increased apoptosis were significantly restored. An in vivo tumorigenesis assay also confirmed that overexpression of Per2 suppresses the growth of OSCC. In conclusion, our research results demonstrate that Per2 suppresses OSCC progression by motivating autophagy, as well as inhibiting cell proliferation and promoting apoptosis, which were mediated by autophagy, in a PI3K/AKT/mTOR pathway-dependent manner. Per2 could potentially be used as a valuable therapeutic marker for OSCC. 

Retracted: No

PubPeer comments:
 This paper is part of a set of 20 short opinion papers that are remarkable mainly because a large proportion of the citations are publications by Dr Faustin Armel Etindele Sosso. In most of these papers about 50-70% of the references are those by Dr. FAES, even though the cited papers sometimes have little to do with the topic of the review. Some of these papers are authored by Dr. FAES himself, while others were written by a group of authors most of whom have never published anything other than papers that heavily cite Dr. FAES. Most of these elusive authors only appear to exist on Research Gate. They cannot be found at the institutes they claim to be affiliated with. They always use a Gmail or Yahoo e-mail address, never an institutional e-mail address for correspondence. More details can be found in this blog post by Nick Brown, who tried very hard - but unsuccessfully - to find these authors: https: steamtraen.blogspot.com 2020 04 the-mystery-of-missing-authors.html Here is a list of the 20 papers, and the percentages of papers in the References written by Dr. FAES. Authors - Title - Citation - Year - DOI - PubPeer link (if DOI) - % FAES citations 1. Faustin Armel Etindele Sosso, Okito Nakamura, Bern Schmidt S, Mitsu Nakamura, Muller G Hito - A novel reflection on sleep disorders approach - Sleep Med Dis Int J. 2017;1(4):79u201280. - 2017 - 10.15406 smdij.2017.01.00016 - https: pubpeer.com publications D50ACF8FCF567EB5C6FEC8DA9EF99A - 67% 2. Muller G Hito - A novel reflection on stigmatization - J Transl Neurosci Vol. 2 No. 1:4. - 2017 - No DOI - NA - 67% 3. Etindele Sosso FA, Nakamura O, and Mitsu N - African burden of Mental Health: necessity of global exchange between researchers - J Adv Res Biotech. 2(2): 1-2 (2017) - 2017 - 10.15226 2475-4714 2 2 00123 - https: pubpeer.com publications E4CD389DA4D2C6ADA89F648F03946C - 100% 4. Nakamura Mitsu, Okito Nakamura and Sana Raouafi - Applications of the Mental Health Profile of Etindele Questionnaire - SM J Sleep Disord. 2017; 3(2): 1012. - 2017 - 10.36876 smjsd.1012 - https: pubpeer.com publications 3EB597DAEBAF3782A9A66D6829731F - 100% 5. Faustin Armel Etindele Sosso, Okito Nakamura and Mitsu Nakamura - Epidemiology of Alzheimeru2019s Disease: Comparison between Africa and South America - J Neurol Neurosci 8:3. (2017) - 2017 - 10.21767 2171-6625.1000204 - https: pubpeer.com publications C26FB2951261F8CF846C45478FF122 - 38% 6. Bern Schmidt S, Eryn Rekgai and Muller G Hito - Hypothesis of Memorisation Process - J Adv Res Biotech 2(3):1-2. (2017) - 2017 - 10.15226 2475-4714 2 3 00125 - https: pubpeer.com publications 359199BCA43E994330D87B3858E289 - 56% 7. Sana Raouafi and Faustin Armel Etindele Sosso - Cyberpsychology: Video games as a perspective for cognitive training - Ment Health Addict Res, 2017 - 2017 - 10.15761 MHAR.1000141 - https: pubpeer.com publications 2155235FEB0201471AF440DF92E6B0 - 19% 8. Faustin Armel Etindele Sosso and Sana Raouafi - An Overview of Positive Interaction between Exercise and Mental Health - J Neurol Neurosci. Vol. 8 No. 4:215 - 2017 - 10.21767 2171-6625.1000215 - https: pubpeer.com publications 8E090D80BE3051A25DBA7287AC8CBF - 26% 9. Bern Schmidt S and Eryn Rekgai - MHPE: An Introduction to a Complete Evaluation Tool - J Transl Neurosci Vol.3 No.1:1 (2018) - 2018 - 10.21767 2573-5349.100014 - https: pubpeer.com publications 3CF90F1C12BC3C549BF5300B1FE288 - 88% 10. Bern Schmidt S and Eryn Rekgai - Stress: Two Sides of a Coin - J Transl Neurosci Vol.3 No.2:5 (2018) - 2018 - 10.21767 2573-5349.100018 - https: pubpeer.com publications BE1E6A295DAE574435E7D006B6E54B - 54% 11. Bern Schmidt and Eryn Rekgai - What is the Path of Sleep Research? - J Neurol Neurosci Vol.9 No.5:268 (2018) - 2018 - 10.21767 2171-6625.1000268 - https: pubpeer.com publications 540CC4447881EA2B9D86B417378DE4 - 55% 12. Faustin Armel Etindele Sosso - Allostastic Load and Allostatic Weight: A Literature Review of a Confusing Concept - J Neurol Neurosci Vol.9 No.1:242. - 2018 - 10.21767 2171-6625.1000242 - https: pubpeer.com publications 7974E47BC3B6B87E31E471CC01DCA7 - 27% 13. Faustin Armel Etindele Sosso - Summary of psychometric properties of the French version of the questionnaire mental health profile of Etindele (MHPE) - Ment Health Addict Res, 2018 - 2018 - 10.15761 MHAR.1000150 - https: pubpeer.com publications EB90E7A056CCF8A4E75533A138A867 - 59% 14. Mustafa El Saad, Mohammed Khalidei, and Muller G. Hito - An Introduction to Appraisal Theories - Archives of Neurology Neurological Disorders (2019) - 2019 - No DOI - NA - 55% 15. Mbraga Theophile, Mitsu Nakamura - Cognitive Performance Opinion - Peer Res Nest. 2019 - 1(1). - 2019 - No DOI - NA - 61% 16. John Okutemo and Mitsu Nakamura - Executive Functions Are Better than IQ? - Arch Neurol Neurol Disord. 2019;2(1):107 - 2019 - No DOI - NA - 61% 17. Carlito Navarro, Romanescu Popei, and Muller G. Hito - Not So Easy to Define Emotional Brain - Arch Neurol Neurol Disord. 2019;2(1):106. - 2019 - No DOI - NA - 50% 18. Janghakar Manshouriyatham and Bern Schmidt - Organic, behavioral or psychosocial? - Arch Neurol Neurol Disord. 2019;2(1):109. - 2019 - No DOI - NA - 57% 19. Okito Nakamura - Simplify the Concept of Cognitive Aging - Peer Res Nest. 2019 - 1(1). - 2019 - No DOI - NA - 64% 20. Okito Nakamura - What is Cognition? - Arch Neurol Neurol Disord. 2019;2(1):105. - 2019 - No DOI - NA - 64% ,