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Yang et al. PANDA, LincRNA-p21, PUMA in Xuanwei

Research has found that PUMA is more important than cell membrane, damage to mitochondria, and mutation
NOXA in DNA damage that induces activation of the in nuclear DNA and mt-DNA.
p53-mediated mitochondrial apoptotic pathway. PUMA
is located downstream of the p53 gene and has a Expression of LincRNA-p21 in lung cancer patients
powerful effect in promoting apoptosis and inhibition from Xuanwei was higher than non-Xuanwei patients
of cell growth. Low expression of PUMA exists in some (P < 0.05). We observed that alveolar epithelial cells
tumor tissues and it is associated with the occurrence and bronchial epithelial cells were severely damaged
and development of tumor. Thus, increasing of PUMA in patients from Xuanwei due to serious air pollution
can inhibit tumor growth. Long non-coding RNA p21 caused by burning of coal. There was also damage to
[11]
interacts with hnRNP-K to activate p21 to enforce cell DNA from pollutants released as a result of combustion
cycle arrest at the G1/S phase. LincRNA-p21 is an of coal. Our initial research in Xuanwei found that ash
important member of the cell cycle and its expression and smoke of bituminous coal contained large numbers
is directly induced by p53. The result of flow cytometry of polyaromatic hydrocarbons and nano-sized quartz
and apoptosis-related enzyme activity assay confirmed particles, [12-14] which were also found in lung tissues
LincRNA-p21 induced apoptosis in the p53 dependent of lung cancer patients from Xuanwei. Polyaromatic
pathway, and related to the formation of tumor. PANDA hydrocarbons and nano-sized quartz particles can lead
is a noncoding RNA that inhibits expression of apoptotic to damage of nuclear DNA and mitochondrial DNA. [15,16]
genes by sequestering NF-YA.
Expression of PUMA in lung tissues of Xuanwei patients
When DNA damage occurs, it activates expression of was lower than non-Xuanwei patients (P < 0.05). The
p53 and LincRNA-p21. In one aspect, the combination correlation analysis revealed that the expression of
of p53 and LincRNA-p21 activates expression of PUMA. LincRNA-p21 had no correlation with expression of
PUMA interact with members of the antiapoptotic PUMA in normal lung tissues of Xuanwei patients,
while normal lung tissues of non-Xuanwei patients
family, and release Bax and Bak. Baxis embedded
in the outer membrane of mitochondria, leading to were positively correlated. We considered that PUMA
increased permeability of the outer mitochondrial is a highly conserved gene in eukaryotes, possibly
membrane. Release of cytochrome C apoptotic factors due to air pollution in Xuanwei causing damage to
activates the caspase cascade, eventually leading to PUMA or effect the gene transcription process, but
also polymorphism of LincRNA-p21 and PUMA in local
cell death.
population could not be ruled out, for which further
This study found that expression of PANDA, research with larger sample is required.
LincRNA-p21 and PUMA showed no significant We have successfully cultured a type of Xuanwei lung
difference in lung tissue of male and female (P > adenocarcinoma cell line (XW-05). We are now carrying
0.05). Expression in squamous cell carcinoma and out gene transfection and silencing experiments on
adenocarcinoma also showed no significant difference XW-05 cells, human adenocarcinoma cells (A549),
(P > 0.05), indicating that there is no gender difference and human bronchial epithelial cells (BS2B) to observe
or tissue specificity. Expression of LincRNA-p21 whether XW-05 cells have specificity.
and PUMA in cancer tissues is not related but in the
normal tissue it is positively correlated, perhaps due to Part of this project was under the U.S. National Cancer
existence of regulatory changes and disorder in cancer Institute to study environmental exposure, dose-
tissues. effect relationship, and epidemiology of lung cancer
in Xuanwei. We are responsible for the questionnaire,
In this study, we found that expression of LincRNA-p21 collection of clinical data, specimen collection,
was higher in patients from non-Xuanwei regions with treatment, follow-up, and prognosis. Genomic
smoking index > 400 than in patients with smoking sequencing is carried out by Beijing Gene Square
index < 400 and non-smokers, while in patients from for National Cancer Institute. Currently, Beijing Gene
Xuanwei, there was no significant difference among Square is sequencing specimens of 421 cases, the
the three groups (P > 0.05). The probable reason might findings of which should be reported soon.
be that smoking is not the main reason for lung cancer
in Xuanwei. The incidence of lung cancer is higher Authors’ contributions
in women from Xuanwei, even though the majority The study’s conception and design: K.Y. Yang, Z.Q.
of women were non-smokers. In an experiment, Shen
we exposed cells to the byproduct obtained from Extraction of RNA and PCR: Y.F. He, K.Y. Yang, K. Rizal
combustion of bituminous coal, the result of which was Patients’ enrollment and lung tissues and data’s
secretion of mediators of inflammation, damage to the collection: K.Y. Yang, A.N. Chen, Y.C. Huang, G.Q.
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ March 27, 2017 69