Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly

Boon, Siaw Shi; Chen, Zigui; Li, Jintao; Ching, Karen Lee Yin; Cai, Liuyang; Zhong, Rugang; Chan, Paul K.S.

doi:10.21203/rs.2.14671/v2

Cited by 4 publications

(7 citation statements)

References 19 publications

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“…We found that in ESCC, HPV18 oncoproteins do not exploit the same mechanism to promote cancer progression as known for cervical cancer. Instead of targeting pRB, E7 preferentially abrogates p130 in EC109 and EC9706, which are the HPV18 containing ESCC cell lines of Asian origin [ 16 ]. In addition to p53 and its downstream transcription transactivator [ 16 ], HPVE6 deregulates miR-125b, a microRNA that acts as a tumour suppressor [ 17 ].…”

Section: Association Between Oncoviruses and Oesophageal Cancermentioning

confidence: 99%

“…Instead of targeting pRB, E7 preferentially abrogates p130 in EC109 and EC9706, which are the HPV18 containing ESCC cell lines of Asian origin [ 16 ]. In addition to p53 and its downstream transcription transactivator [ 16 ], HPVE6 deregulates miR-125b, a microRNA that acts as a tumour suppressor [ 17 ]. The downregulation of miR-125b may subsequently lead to activation of the Wnt/β-catenin signaling pathway, which is a critical pathway involved in cell differentiation, migration, proliferation, and cell death.…”

Section: Association Between Oncoviruses and Oesophageal Cancermentioning

confidence: 99%

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Oesophageal carcinoma: The prevalence of DNA tumour viruses and therapy

Luk

Xia

et al. 2022

Tumour Virus Research

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Oesophageal carcinoma ranks the sixth leading cause of cancer death and affected 544,000 - 604,000 people in 2020. Patients often presented with a poor cancer prognosis with a low survival rate of 15–25%. Depending upon the cell type, oesophageal carcinoma is categorised into oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC). ESCC is predominantly reported in developing countries, while EAC is more common in developed countries. Aside from the presence of exogenous co-factors, such as cigarette smoking, alcohol consumption, obesity, gastroesophageal reflux disease (GERD); infection with oncogenic viruses is suspected to be one of the major factors contributing to EC development. Oncogenic viruses, including human papillomavirus (HPV), Epstein Barr virus (EBV), Cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) have been detected in various proportions of EC samples. Nonetheless, their aetiological roles in EC remain debatable. In this review, we garnered previous studies that focus on the association between oncogenic viruses and EC. Among these oncogenic viruses, HPV appears to have a stronger association with EC than the others. In addition, we also discuss the pros and cons of the treatment regimens to treat EC patients, including immunotherapy, chemo- and chemoradiotherapy, and their efficacy.

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Section: Association Between Oncoviruses and Oesophageal Cancermentioning

confidence: 99%

Section: Association Between Oncoviruses and Oesophageal Cancermentioning

confidence: 99%

Oesophageal carcinoma: The prevalence of DNA tumour viruses and therapy

Luk

Xia

et al. 2022

Tumour Virus Research

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“…The fundamental aspects of cancer biology consist of the cell dysregulation of proliferation, cell apoptosis [ 30 ], metastasis [ 31 ], gene aberration [ 32 ], anchorage-independent growth (AIG) [ 33 ], and tumor formation. Studies have found that HPV E6 mediates downregulation of p53, leading to DNA damage [ 34 – 36 ]. HPV E7 protein could downregulate the expression of p21 and p27, affect the cell cycle and make cells overproliferate, and result in inducing the occurrence of tumors [ 34 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have found that HPV E6 mediates downregulation of p53, leading to DNA damage [ 34 – 36 ]. HPV E7 protein could downregulate the expression of p21 and p27, affect the cell cycle and make cells overproliferate, and result in inducing the occurrence of tumors [ 34 , 36 , 37 ]. In our study, p21 was definitely downregulated.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

Zhang

Zhao

et al. 2020

Oxidative Medicine and Cellular Longevity

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N-methyl-N´-nitro-N-nitrosoguanidine is a clear carcinogen, increasing evidence that indicates an etiological role of human papillomavirus in esophageal carcinoma. Studies have reported the synergistic effect on environmental carcinogens and viruses in recent years. On the basis of establishing the malignant transformation model of Het-1A cells induced by synergistic of HPV18 and MNNG, this study was to explore the synergistic carcinogenesis of MNNG and HPV. Our research indicated that HPV&MNNG led to a significant increase in the protein-expression levels of c-Myc, cyclinD1, BCL-2, BAX, E-cadherin, N-cadherin, mTOR, LC3II, and p62, with concomitant decreases in p21 and LC3I. HPV18 and MNNG induced accumulation of p62 and its interaction with KEAP1, which promoted NRF2 nuclear translocation. p62 loss prevents growth and increases autophagy of malignant cells by activating KEAP1/NRF2-dependent antioxidative response. In addition, PI3K and p-AKT were stimulated by HPV&MNNG, and PI3K/AKT/mTOR is positively associated with cell proliferation, migration, invasion, and autophagy during malignant transformation. Taken together, MNNG&HPV regulates autophagy and further accelerates cell appreciation by activating the p62/KEAP1/NRF2 and PI3K/AKT/mTOR pathway. MNNG&HPV may improve Het-1A cell autophagy to contribute to excessive cell proliferation, reduced apoptosis, and protection from oxidative damage, thus accelerating the process of cell malignant transformation and leading to cancerous cells.

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“…Consumption of CBX3 by lentivirus‐mediated shRNA resulted in cell cycle delay by upregulating the P21 pathway (H. Zhang, Chen, Fu, Su, & Yang, 2018). It is documented that P21 acts as a downstream transactivation target of P53 (Boon et al, 2019). Moreover, a study conducted by Natsugoe et al (1999) revealed that P21 expression was positively correlated with P53 in ESCC tissues.…”

Section: Discussionmentioning

confidence: 99%

microRNA‐377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3‐dependent P53/P21 pathway

Chen

et al. 2020

Journal Cellular Physiology

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Stem cells play pivotal roles in esophageal squamous cell carcinoma (ESCC) recurrence and metastasis. The self-renewal ability of stem cells was associated with specific microRNAs (miRs). Herein, we identified the effects of miR-377 on ESCC stem cell activities. First, the expression of miR-377 in ESCC and adjacent normal tissues was determined. The relationship between miR-377 and chromobox protein homolog 3 (CBX3) was assessed by a dual-luciferase reporter gene assay. miR-377 was overexpressed or inhibited in ESCC stem cells to explore its role in ESCC. To further investigate the mechanism of miR-377 in ESCC, cells were introduced with short hairpin RNA against CBX3 or pifithrin-α (inhibitor of P53 pathway). Besides, the expression of P21, P53, CD133, CD13, Nanog, sex determining region Y-Box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4), cell sphere formation, colony formation, and proliferation were evaluated respectively. Finally, limiting dilution assay in vivo and tumor xenograft in nude mice were conducted to confirm the roles of miR-377 in vivo. miR-377 was poorly expressed in ESCC. Overexpression of miR-377 could suppress the stem-like trait of ESCC as well as the tumor growth in vivo. miR-377 targeted CBX3 to activate the P53/P21 pathway. Besides, the expression of stem-like markers including CD133, CD13, Oct4, Sox2, and Nanog was decreased, and the abilities of cell sphere formation, colony formation, proliferation, and tumorigenicity were significantly reduced by overexpressing miR-377 or silencing CBX3. The results were reversed after inactivating the P53/P21 pathway. In summary, upregulation of miR-377 inhibits the self-renewal of ESCC stem cells by inhibiting CBX3 expression and promoting activation of the P53/P21 pathway.

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Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly

Cited by 4 publications

References 19 publications

Oesophageal carcinoma: The prevalence of DNA tumour viruses and therapy

Oesophageal carcinoma: The prevalence of DNA tumour viruses and therapy

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

microRNA‐377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3‐dependent P53/P21 pathway

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