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LincRNA-p21 Suppresses Glutamine Metabolism And Bladder Cancer Cell Growth Through Inhibiting Glutaminase Expression

Posted on:2020-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:Q ZhouFull Text:PDF
GTID:2404330575987076Subject:Surgery
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Background Bladder cancer is a malignant tumor on the origin from urothelial epithelium tissue,the incidence of bladder cancer ranks the first among the malignant tumors of the urinary system in China,while in foreign countries,its incidence is second only to prostate cancer.It is the most common malignant tumor in the urinary and reproductive system and one of the top ten malignant tumors of the whole body.Although with the development of medical technology and medical means,there is still a lack of effective treatment for bladder cancer.Currently,surgery is still suitable for early and metaphase bladder cancer patients,but it's still a high risk of recurrence after surgery.Patients with advanced bladder cancer who always appear invasion of adjacent tissues or lymph node metastasis,surgical treatment has unable to resects the lesion,with palliative treatment measures such as radiotherapy,chemotherapy or immunotherapy are used.In the process of treatment,the mortality rate is high,which cause heavy economic and psychological burden to the patients.According to the epidemiological survey,the incidence of bladder cancer is increasing year by year,and it has become a major public health problem that seriously endangers human life and health.However,the etiology of bladder cancer is very complicated,which not only has its own genetic factors,but also has the influence of environmental factors.With the in-depth research of genome sequencing,massive data of interconnection and mutual regulation between genes have been obtained rapidly and accurately,revealing the logical relationship between genes or gene products,and clarifying that gene expression regulation does not exist in a single and isolated way,but is interrelated and mutually restricted.Therefore,it is of great clinical significance to further study the molecular biological mechanism in the development process of bladder cancer and explore new targets for the diagnosis and treatment of bladder cancer.Long non-coding RNA(lncRNA)is a type of RNA molecule with a length of over 200 nt that is transcribed from the genome.However,lncRNA molecules do not play a role through the translation of coding proteins.It's a mistake to think of Lnc RNA molecules as the noise in the transcription process.With the further development of gene research,lncRNA has been recognized by people again.A large number of studies have reported that lncRNA plays an important role in gene expression regulation,participates in the occurrence and development of tumor and other diseases,and plays an important regulatory role.Long intergenic non-coding RNA(lincRNA)is a kind of long non-coding RNA that exists between genes,which is closely related to the intrinsic molecular mechanism of diseases such as tumors.Glutamine metabolism is considered to be a significant feature of cancer,in which cancer cells obtain energy and nutrients to support the growth and proliferation of cancer cells.In addition,glutamine metabolism is influenced by some oncogenes or tumor suppressor genes in cells,and glutaminase(GLS)is a key enzyme in the regulation of glutamine metabolism.Therefore,the study on the effect of long non-coding RNA on glutaminase may find a potential new target for the diagnosis and treatment of bladder cancer,but this still needs to be further verified by objective scientific experiments and clinical practice.Objective To study the expression and biological function of lincRNA-p21 in bladder cancer tissues and cell lines,and to explore the mechanism of lincRNA-p21 affecting the biological function of bladder cancer.Methods The expression levels of lincRNA-p21 and GLS in bladder cancer tissues and bladder cancer cell lines were detected by real-time quantitative PCR(q RT-PCR).Bladder cancer cell lines were transfected with specific lincRNA-p21 and GLS small interfering RNA(si RNA)and overexpressed plasmid vectors.CCK and clonal formation experiments were performed to verify the growth and proliferation of bladder cancer cells.The expression of GLS and its metabolites were detected by q RT-PCR and Western blot.Results In bladder cancer tissue samples,the expression level of lincRNA-p21 was significantly lower than that of the matched paracancerous normal tissue(P < 0.01),on the contrary,the expression level of GLS was significantly higher than that of the paired paracancerous tissue(P < 0.01).Overexpression of lincRNA-p21 significantly inhibits the proliferation of bladder cancer cells(P < 0.05)and growth(P < 0.01),as well as glutaminase expression(P < 0.05),thereby inhibiting glutamine metabolism(P < 0.05)and metabolites(P < 0.05).In contrast,silencing lincRNA-p21 promotes the proliferation of bladder cancer cells(P < 0.05)and growth(P < 0.01),as well as glutaminase expression(P < 0.05),thereby increasing glutamine metabolism(P < 0.05)and metabolites(P < 0.05).Conclusion The expression level of lincRNA-p21 in bladder cancer cell lines and bladder cancer tissues was relatively low,suggesting that lincRNA-p21 may be related to tumor inhibition.Linc RNA-p21 plays a biological role in inhibiting the proliferation and growth of bladder cancer cells and is involved in the biological regulation of the growth and proliferation of bladder cancer cells.Linc RNA-p21 plays a role of tumor suppressor gene in bladder cancer.It may become a potential new target for the diagnosis and treatments of bladder cancer and provide a favorable research direction for the diagnosis and treatments of bladder cancer.
Keywords/Search Tags:bladder cancer, lincRNA-p21, glutamine metabolism, GLS
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