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The Function And Mechanism Between Long-non Coding RNA MALAT1 And Clinicopathologic Characteristics And Effect Of Radiotherapy On Cervical Cancer

Posted on:2019-12-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:1364330548956470Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective:(1)To investigate the expression level of long non-coding RNA MALAT 1 in cervical squamous carcinoma and normal tissue samples,and to evaluate the relationship between MALAT 1 and clinical pathological features,radiation sensitivity and prognosis of cervical squamous carcinoma.(2)Four types of cervical cancer cell lines,Hela,CaSki,SiHa,HCC 94,and human immutative epidermal cell HaCAT were selected.The expression of MALATl in HeLa Ski,SiHa,HCC 94,Ha CAT was detected by RT-PCR.The function of MALAT 1 was further understood by screening and selecting the two highest expression lines,HeLa and CaSki.(3)The mechanism of MALAT 1 in cervical cancer was clarified by detecting phosphorylation levels of two cell lines,HeLa and CaSki,and the effect of MALAT 1 on radiation was studied by local radiotherapy after epiderma in mice.Methods:(1)The expression of MALAT 1 was detected by RT-PCR in 60 cases of cervical squamous carcinoma and 30 cases of normal cervical specimens.The clinical and pathological features,radiation sensitivity and survival data were analyzed.(2)The high expression cell lines of HeLa and CaSki were screened by using Hela,CaSki,SiHa,HCC 94 and HaCaT as human epidermal cells to determine MALAT1 expression.(3)The key pathways of the silent MALAT1 cervical cancer cell line were detected by using the Western-blotting test,and the mechanism of regulating cell growth was explored.CaSki/NC and CaSki/si-M1 were planted under the skin of mice.The growth of plantomas before and after radiotherapy was compared with local radiotherapy.Results:(1)The expression of MALAT 1 increased in cervical cancer tissue.The expression of MALAT 1 was significantly correlated with tumor stage and lymph node metastasis.The increase in MALAT 1 was associated with poor sensitivity to radiation in cervical cancer patients.The low expression of MALAT 1 was associated with a longer survival period in cervical cancer patients than the high expression of MALAT 1.(2)Four types of cervical cancer cells,Hela,CaSki,SiHHA,HCC 94 and HaCa T,respectively.The expression levels of MALATl in HeLa,CaSki,SiHa,HCC 94,HaCaT were detected by RT-PCR and the two most expressed cell lines,HeLa and CaSki,were screened.Silent MALAT 1 could inhibit the proliferation,colony formation and invasion of HeLa and CaSKi cells.(3)Silent MALAT 1 activates the levels of phosphorylation of ATM-CHK2 in the HeLa and CaSKi cells,further suggesting that MALAT 1 is carcinogenic by activating the ATM-CHK2 pathway.CaSki/si-M1 cells in the experimental group expressed by silent MALAT 1 decreased significantly after radiotherapy compared with control CaSki/NC cells.Conclusion: Through this experiment,we first verified that MALAT 1 is a carcinogenic gene in cervical squamous carcinoma.Silence MALAT 1 activated the levels of phosphorylation of ATM-CHK2 in HLa and CaSKi cells,deepened the understanding of MALAT 1,a new regulator,and further clarified the pathogenesis of cervical cancer.
Keywords/Search Tags:Long non-coding RNA MALAT1, Cervical Cancer, Clinicopathologic characteristics, Effect of radiotherapy, The function and mechanism
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