MID1–PP2A complex functions as new insights in human lung adenocarcinoma
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MID1 is an E3 ubiquitin ligase that was first found in Opitz G/BBB syndrome, but there has been little research into its role in lung diseases. We have found an accumulating evidence that indicates the MID1–PP2A complex plays a role in asthma and contributes to inflammation, but its roles in lung adenocarcinoma are unclear. This study aimed at evaluating the function of MID1–PP2A complex in human lung adenocarcinoma.
We used western blot, ELISA and real-time quantitative PCR to detect the protein and mRNA levels of MID1 and PP2A in A549, H1975, and H1650 lung adenocarcinoma cell lines compared with the human bronchial epithelial cell line BEAS-2B. Additionally, we used IHC, ELISA and real-time quantitative PCR to dectect MID1 and PP2A levels in 30-paired lung adenocarcinoma tissues. We also detected apoptosis, proliferation and cell cycle-related protein expression after silencing MID1 and activing PP2A.
Our data show that MID1 was significantly upregulated in 30-paired lung adenocarcinoma tissues, and in A549, H1975 and H1650 cell lines compared with BEAS-2B. PP2A showed the opposite results. Furthermore, both upregulated MID1 and downregulated PP2A were correlated with age, but not sex, TNM stage or smoking history. In vitro experiments showed that PP2A was upregulated in lung adenocarcinoma cell lines that were transfected with MID1-siRNA, suggesting MID1 negatively regulates PP2A in lung adenocarcinoma. We also found that silencing MID1 expression or activating PP2A induced apoptosis, proliferation and cell cycle arrest.
We demonstrated that the MID1–PP2A complex plays an important role in lung adenocarcinoma, influencing cell cycle progression, proliferation and apoptosis. Our findings showed a novel molecular mechanism of lung tumorigenesis that may provide new insights for anti-tumor therapies.
KeywordsMID1 PP2A Lung adenocarcinoma Apoptosis Cell cycle Proliferation
The authors wish to thank the Second Affiliated Hospital of Jilin University, as well as the patients and their families.
JZ contributed to the conception of the study. JL, XL, TG and WL contributed significantly to analysis and manuscript preparation; LZ finished the experiments, performed the data analyses and wrote the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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