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

           Table 5: Expression of LincRNA-p21, PANDA and PUMA in squamous cell carcinoma and adenocarcinoma
            Gene                                 Adenocarcinoma       Squamous cell carcinoma         P
            LincRNA-p21       Xuanwei            15.23 ± 1.31         15.09 ± 1.53                   0.56
                              Non-Xuanwei        12.31 ± 1.73         12.18 ± 2.05                   0.58
            PANDA             Xuanwei            14.38 ± 1.64         14.22 ± 1.88                   0.74
                              Non-Xuanwei        14.11 ± 1.31         14.01 ± 2.15                   0.82
            PUMA              Xuanwei            5.09 ± 1.15          5.33 ± 1.84                    0.64
                              Non-Xuanwei        7.39 ± 1.98          7.36 ± 2.76                    0.86

           Table 6: Expression of LincRNA-p21, PANDA, PUMA in smokers and non-smokers
            Gene                                 Non-Smoker            Smoking < 400       Smoking > 400
            LincRNA-p21       Xuanwei            15.19 ± 1.01          15.14 ± 1.21        15.16 ± 2.02
                              Non Xuanwei        12.95 ± 2.13          13.16 ± 1.73        14.74 ± 2.11*
            PANDA             Xuanwei            14.37 ± 1.21          14.37 ± 1.53        14.38 ± 1.74
                              Non Xuanwei        14.08 ± 0.88          14.15 ± 1.29        14.14 ± 1.29
            PUMA              Xuanwei            5.31 ± 1.47           5.33 ± 1.91         5.32 ± 1.12
                              Non Xuanwei        7.31 ± 1.82           7.33 ± 1.46         7.34 ± 2.05
           *P < 0.05 (comparing non-smokers with smokers with smoking index < 400 and > 400)
           DISCUSSION                                         Table 7: Expression of LincRNA-p21, PANDA and PUMA
                                                              in lung cancer patients from Xuanwei
           The Xuanwei  region  of  Yunnan,  China,  has a high                            Spearman correlation
           incidence of lung cancer.  The characteristics of lung   Gene     Tissue type       R         P
                                  [2]
           cancer in Xuanwei are: (1) the mortality rate of lung   LincRNA-p21   Cancer tissue  0.08    0.62
           cancer in Xuanwei was 28.20/100,000 in 1973-1975,   and PUMA      Normal tissue    0.12      0.33
                                                                                              0.07
                                                                             Cancer tissue
                                                               PANDA and
                                                                                                        0.58
           in 1990-1992 it was 40.29/100,000, and in 2004-2005   PUMA        Normal tissue    0.14      0.28
           it  was 83.28/100,000, which were higher than the   LincRNA-p21   Cancer tissue    0.81      0.00
           average of the entire Yunnan and the national average;   and PANDA  Normal tissue  0.77      0.00
           (2) lung cancer caused death 10-15 years earlier than   Table 8: Expression of LincRNA-p21, PANDA and PUMA
           the national average age; (3) lung cancer incidence is   in lung cancer patients from non-Xuanwei areas
           high among female population whereas the sex ratio                              Spearman correlation
           (male:female)  is low  in other places  like  Netherland   Gene   Tissue type      R         P
           (16.32), Sweden (4.15), China (2.01), whereas in it is   LincRNA-p21   Cancer tissue  0.06  0.67
           1.09. In the small town of Laibin in Xuanwei the sex ratio   and PUMA  Normal tissue  0.35  0.04
           for the incidence of lung cancer is 0.87, with females   PANDA and   Cancer tissue  0.08    0.62
                                                                                             0.42
                                                                                                       0.00
                                                                             Normal tissue
                                                               PUMA
           being affected more than males; (4) the incidence of   LincRNA-p21   Cancer tissue  0.84    0.00
           lung cancer in Xuanwei area may be familial.        and PANDA     Normal tissue   0.71      0.00
           Indoor burning of bituminouscoal, leading to indoor air   through mitochondrial  caspase. [8,9]  It  is well known
           pollution, is considered to be the main reason for the   that repeated DNA damage can be carcinogenic, and
           high incidence of lung cancer in Xuanwei. Polyaromatic   tumor suppressor p53 increases as a response to DNA
           hydrocarbons (PAHs), nano silica particles and other   damage. Burning of coal produces numerous harmful
           substances in bituminouscoal  dust and smoke are   pollutants and carcinogens which causes damage to
           thought to be the causes of lung cancer. [6,7]  In 1970,   DNA. At the molecular level, DNA damage is sensed
           the Chinese government implemented a policy at all   by  human protein kinase ATM  (ataxia-telangiectasia,
           levels to improve coal burning stoves which could lead   mutated), leading  to phosphorylation  and  activation
           to improvement  of indoor  air quality. Despite  these   of ATM.  Downstream phosphorylation  and activation
           efforts, lung cancer incidence is still high and with an   of TP53, together with RUNX3, activate transcription
           increasing trend.                                  of downstream mediators  as a response  to injury  to
                                                              DNA. [10]
           The development  of lung  cancer  is a complex
           biological process which is multistep and multifactorial.   In our previous study with 25 patients of lung cancer
           It not only includes the activation and inactivation of   (adenocarcinoma  and squamous cell cancer) from
           oncogenes  and tumor suppressor gene  respectively,   Xuanwei, we found differences in 33 genes, of which
           but  also has close relationship  with apoptosis.   LincRNA-p21 was one of them. As a result, we chose
           There are two pathways of  apoptosis of  which one   to  study  LincRNA-p21. In  this  study,  we focused on
           is the activation of  the apoptotic caspase through   three selected mediators of  TP53 response: PUMA,
           extracellular  signaling  while  the other is release  of   LincRNA-p21 and PANDA. PUMA is a member of the
           cytochrome  C and  activation  of apoptotic  enzyme   BCL2 family and is an important mediator of apoptosis.
            68                                                                    Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ March 27, 2017
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