PMID- 32499837
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220414
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 12
DP  - 2020
TI  - HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the 
      effect of LKB1 on Sp1 phosphorylation in lung cancer cells.
PG  - 1758835920917562
LID - 10.1177/1758835920917562 [doi]
LID - 1758835920917562
AB  - BACKGROUND: There is an immediate need for research on the mechanism underlying 
      telomerase activation and overexpression. MATERIALS & METHODS: A total of 174 
      patients with lung cancer (n = 106) and benign lung disease (n = 68) were 
      recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, 
      and hTERC in brushing cells were detected by quantitative reverse transcriptase 
      polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by 
      fluorescence in situ hybridization (FISH). To investigate the potential 
      mechanism, bidirectional genetic manipulation was performed in well-established 
      lung cancer cell lines. RESULTS: Our results indicated that the mRNA expression 
      levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were 
      significantly increased in the malignant group compared with those of the benign 
      group (p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly 
      decreased in the malignant group (p < 0.01). The correlation between E6, E7, Sp1, 
      and hTERC expression was positive but was negative with LKB1 (p < 0.01). Our 
      results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both 
      the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and 
      also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene 
      amplification levels. Thus, we proposed a HPV-LKB1-Sp1-hTERC axis of E6/E7 
      upregulation of hTERC expression. CONCLUSION: We demonstrated for the first time 
      that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by 
      relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated 
      hTERC by directly binding to the promoter regions of hTERC.
CI  - (c) The Author(s), 2020.
FAU - Yang, Jing-Hua
AU  - Yang JH
AUID- ORCID: 0000-0001-6813-9672
AD  - Department of Pathology, The First Affiliated Hospital and College of Basic 
      Medical Sciences, China Medical University, Shenyang, China.
FAU - Wu, Ming-Zhe
AU  - Wu MZ
AD  - Department of Gynecology, The First Hospital of China Medical University, 
      Shenyang, China.
FAU - Wang, Xu-Bo
AU  - Wang XB
AD  - Department of Pathology, Xuzhou City Hospital of TCM, Nanjing University of 
      Chinese Medicine, Xuzhou, China.
FAU - Wang, Shiyu
AU  - Wang S
AD  - Geisinger Commonwealth School of Medicine, Scranton, PA, USA.
FAU - Qiu, Xue-Shan
AU  - Qiu XS
AD  - Department of Pathology, The First Affiliated Hospital and College of Basic 
      Medical Sciences, China Medical University, Shenyang, China.
FAU - Wang, En-Hua
AU  - Wang EH
AD  - Department of Pathology, The First Affiliated Hospital and College of Basic 
      Medical Sciences, China Medical University, Shenyang, China.
FAU - Wu, Guang-Ping
AU  - Wu GP
AUID- ORCID: 0000-0003-3478-6868
AD  - Department of Pathology, The First Affiliated Hospital and College of Basic 
      Medical Sciences, China Medical University, No.155 Nanjing Bei Street, Shenyang 
      110001, China.
LA  - eng
PT  - Journal Article
DEP - 20200512
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC7243384
OTO - NOTNLM
OT  - RNA component of human telomerase gene
OT  - human papillomavirus (HPV)
OT  - liver kinase B1
OT  - lung cancer
OT  - specificity protein 1
COIS- Conflict of interest: The authors declare that there is no conflict of interest.
EDAT- 2020/06/06 06:00
MHDA- 2020/06/06 06:01
PMCR- 2020/05/12
CRDT- 2020/06/06 06:00
PHST- 2019/01/22 00:00 [received]
PHST- 2020/03/04 00:00 [accepted]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2020/06/06 06:01 [medline]
PHST- 2020/05/12 00:00 [pmc-release]
AID - 10.1177_1758835920917562 [pii]
AID - 10.1177/1758835920917562 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2020 May 12;12:1758835920917562. doi: 
      10.1177/1758835920917562. eCollection 2020.