PMID- 35884433
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 14
DP  - 2022 Jul 11
TI  - PRIM2 Promotes Cell Cycle and Tumor Progression in p53-Mutant Lung Cancer.
LID - 10.3390/cancers14143370 [doi]
LID - 3370
AB  - p53 is a common tumor suppressor, and its mutation drives tumorigenesis. What is 
      more, p53 mutations have also been reported to be indicative of poor prognosis in 
      lung cancer, but the detailed mechanism has not been elucidated. In this study, 
      we found that DNA primase subunit 2 (PRIM2) had a high expression level and 
      associated with poor prognosis in lung cancer. Furthermore, we found that PRIM2 
      expression was abnormally increased in lung cancer cells with p53 mutation or 
      altered the p53/RB pathway based on database. We also verified that PRIM2 
      expression was elevated by mutation or deletion of p53 in lung cancer cell lines. 
      Lastly, silence p53 increased the expression of RPIM2. Thus, these data suggest 
      that PRIM2 is a cancer-promoting factor which is regulated by the p53/RB pathway. 
      The p53 tumor-suppressor gene integrates numerous signals that control cell 
      proliferation, cell cycle, and cell death; and the p53/RB pathway determines the 
      cellular localization of transcription factor E2F, which regulates the expression 
      of downstream targets. Next, we explored the role of PRIM2 in lung cancer and 
      found that knockdown of PRIM2 induced cell cycle arrest, increased DNA damage, 
      and increased cell senescence, leading to decreased lung cancer cell 
      proliferation. Lastly, the positive correlation between PRIM2 and E2F/CDK also 
      indicated that PRIM2 was involved in promoting cell cycle mediated by p53/RB 
      pathway. These results confirmed that the expression of PRIM2 is regulated by the 
      p53/RB pathway in lung cancer cells, promotes DNA replication and mismatch 
      repair, and activates the cell cycle. Overall, we found that frequent p53 
      mutations increased PRIM2 expression, activated the cell cycle, and promoted lung 
      cancer progression.
FAU - Wang, Taoyuan
AU  - Wang T
AD  - Clinical School of Thoracic, Tianjin Medical University, Tianjin 300070, China.
FAU - Tang, Tiansheng
AU  - Tang T
AD  - Clinical School of Thoracic, Tianjin Medical University, Tianjin 300070, China.
FAU - Jiang, Youguo
AU  - Jiang Y
AD  - Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, 
      Tianjin 300052, China.
FAU - He, Tao
AU  - He T
AD  - Departments of Pathology, Characteristic Medical Center of the Chinese People's 
      Armed Police Force, 220 Chenglin Road, Dongli District, Tianjin 300162, China.
FAU - Qi, Luyu
AU  - Qi L
AD  - Cardiothoracic Surgery Department, Characteristic Medical Center of the Chinese 
      People's Armed Police Force, 220 Chenglin Road, Dongli District, Tianjin 300162, 
      China.
FAU - Chang, Hongkai
AU  - Chang H
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 
      300350, China.
FAU - Qiao, Yaya
AU  - Qiao Y
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 
      300350, China.
FAU - Sun, Mingming
AU  - Sun M
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 
      300350, China.
FAU - Shan, Changliang
AU  - Shan C
AUID- ORCID: 0000-0002-4906-1686
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 
      300350, China.
FAU - Zhu, Xinyuan
AU  - Zhu X
AD  - Department of Cardiovascular Surgery, Tianjin Medical University General 
      Hospital, Tianjin 300052, China.
FAU - Liu, Jianshi
AU  - Liu J
AD  - Department of Cardiovascular Surgery, Tianjin Chest Hospital, Tianjin 300222, 
      China.
FAU - Wang, Jiyan
AU  - Wang J
AUID- ORCID: 0000-0002-0518-8626
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and 
      Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 
      300350, China.
LA  - eng
GR  - 81973356/National Nature Science Foundation of China/
GR  - 21JCZDJC00060/Natural Science Foundation of Tianjin/
GR  - 3206054, 91923101, 63213082, and 92122017/The Fundamental Research Funds for the 
      Central Universities of Nankai University/
PT  - Journal Article
DEP - 20220711
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9320259
OTO - NOTNLM
OT  - PRIM2
OT  - cell cycle
OT  - lung cancer
OT  - mismatch repair
OT  - p53 mutation
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/11
CRDT- 2022/07/27 01:10
PHST- 2022/05/31 00:00 [received]
PHST- 2022/07/07 00:00 [revised]
PHST- 2022/07/08 00:00 [accepted]
PHST- 2022/07/27 01:10 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/11 00:00 [pmc-release]
AID - cancers14143370 [pii]
AID - cancers-14-03370 [pii]
AID - 10.3390/cancers14143370 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Jul 11;14(14):3370. doi: 10.3390/cancers14143370.