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Published on: July 21, 2018
GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer
Xiumei Sheng1,2, Nathan Bowen2, Zhengxin Wang3
1School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.
Background:
GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1's role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized.
Methods:
DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed.
Results:
We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3).
Conclusions:
This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer.
Insights
This study shows Protein arginine methyltransferase 5 (PRMT5) and WDR77 regulate GLI pathogenesis-related 1 (GLIPR1) expression, impacting lung cancer cell growth. GLIPR1 acts as a tumor suppressor and potential therapeutic target in lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- GLI pathogenesis-related 1 (GLIPR1) exhibits tumor-suppressive and pro-apoptotic functions, but its role in lung cancer is uncharacterized.
- Protein arginine methyltransferase 5 (PRMT5) and WDR77 are crucial for lung cancer cell proliferation, with their interacting partners yet to be fully identified.
Purpose of the Study:
- To investigate the role of GLIPR1 in lung cancer.
- To identify novel regulators of lung cancer cell growth involving PRMT5 and WDR77.
Main Methods:
- DNA microarray and immunostaining analyzed GLIPR1 expression in lung development and tumorigenesis.
- GLIPR1 expression was assessed in the TCGA lung cancer cohort.
- The impact of GLIPR1 on lung cancer cell growth was evaluated in vitro and in vivo xenograft models.
Main Results:
- GLIPR1 expression inversely correlates with PRMT5/WDR77 levels.
- GLIPR1 expression is downregulated during lung tumorigenesis and suppresses lung cancer cell growth.
- GLIPR1 mediates its effects on lung cancer growth via ErbB3 signaling.
Conclusions:
- A novel pathway where PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth is identified.
- GLIPR1 emerges as a potential therapeutic agent for lung cancer treatment.
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