The Expression And Regulation Of The Molecular Mechanisms Of Heat Shock Transcription Factor 2 In Lung Cancer

Lung cancer is the world's one of the most common malignant tumor,its mortality was highest in all malignant tumor.Therefore,the way of improving the prognosis of lung cancer is early diagnosis.However,early diagnosis of lung cancer depended on the research progress of pathology;and thus,looking for biomarkers for early diagnosis of lung cancer and exploring the biological basis of tumorigenesis and tumor progression has a great significance.HSF2,an important member of heat shock factors(HSF),can resistant to thermal stimulation;in addition,it is more sensitive to the growth,development and differentiation signal,and it can regulation of the embryonic development.However,few studies focused on the role HSF2 in cancers.Whether HSF2 participates in the occurrence and development of cancer,and the relationship between HSF2 and cancer was not clear.The main results of this thesis were as follows:(1)HSF2 gene expression level in lung cancer tissues was significantly higher than that normal control group's expression level,the difference was statistically significant.We used 50 cases and its corresponding adjacent tissue which were collected from Kunhua hospital.We found that among the 50 cases,40 cases' mRNA raised obviously and 38 cases' protein increased obviously,while there was notany high expression in the corresponding adjacent tissue.Compared the tumor and normal groups,the difference was statistical significance.On the other hand,we used the gene expression data from The Cancer Genome Atlas(TCGA)database(445 lung adenocarcinoma samples and 58 normal controls,408 lung squamous carcinoma samples and 51 normal controls)to further explore the relationship between HSF2 and lung cancer.We found that HSF2 gene expression level in lung cancer samples was also higher expression than the normal controls.The above results suggested that HSF2 gene involves in the formation and development of lung cancer.(2)HSF2 gene expression level was no significance differences in the clinical characteristics of lung cancer.In the 50 lung cancer samples and the samples from TCGA database,HSF2 gene expression level was no significant difference in different age,different gender,smoking historyand different degree of differentiation..At the same time,we found there was no significant relationship between HSF2 gene expression level and prognosis recurrence time and prognosis of total survival time of lung adenocarcinoma people.Meanwhile,there also did not exist any relationship a between HSF2 gene expression level and prognosis of prognosis recurrence time and prognosis of total survival time of lung squamous carcinoma people.(3)HSF2 has the ability to promote cell proliferation and migration.The proliferation and migration of BEAS-2B cell with HSF2 vector was velocity quickened significantly.On the contrary,when used shRNA interference HSF2 expressing,the proliferation and migration of A549 and SK-MES-1 cells was velocity significantly slower than the group which did not interfere with shRNA.(4)The ability of HSF2 to promote cell proliferation and migration depends on the presence of HSF1.When HSF1 is interfered by shRNA,the ability of HSF2 to promote cell proliferation and migration is inhibited,suggesting that the ability of HSF2 to promote cell proliferation and migration depends on HSF1 function.(5)The ability of HSF2 to promote cell proliferation and migration is via promoting the expression of HSPs.When interfering with a member of the HSPs,the ability of HSF2 to promote cell proliferation and migration was inhibited,and the effect was most pronounced when interfering with HSP27,HSP70 or HSP90.It can be seen that the ability of HSF2 to promote cell proliferation and migration depends on the expression of HSPs.(6)HSF2 promoting cell proliferation and migration through JNK signaling pathway and the Akt.Through increasing the related proteins'level which led by p-Akt protein and decreasing the apoptosis-related proteins'level which led byp-JNK protein,HSF2 can promote the proliferation and migration of cells.(7)Between the lung cancer group and normal control group,the frequency of HSF2 gene promoter methylation has no significant difference.When use DNA methylation data of lung adenocarcinoma and lung squamous cell carcinomas from TCGA database for analysis,we found that not only in cancer samples but also in normal control samples,the frequency of HSF2 gene promoter methylation had no significant difference.The frequency of HSF2 gene promoter methylation was very low in the both group(lung adenocarcinoma and lung squamous cell carcinomas).Meanwhile,in the 50 cases of lung cancer and its corresponding adjacent tissue,we found that the frequency of HSF2 gene promoter methylation was very low and there was no significant difference between cancer and normal samples.In our study,we system explored the relationship between expression level of HSF2 and lung cancer,and expounded that the mechanism of HSF2 promotes cell proliferation and migration.We concluded that the HSF2 was closely related to formation and development of lung cancer.Through Akt and JNK signaling.HSF2 can promote cell proliferation and migration,suppresses cell apoptosis,and then promote the formation and development of lung cancer.However,for the difference expression level of HSF2 in lung cancer and normal controls need further study.