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Role Of LncNONHSAT028712 In Breast Cancer

Posted on:2021-04-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y CuiFull Text:PDF
GTID:2404330611973309Subject:Public Health and Preventive Medicine
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At present,breast cancer in China ranks first in the incidence of cancer in women and fifth in the number of cancer deaths among women.Breast cancer not only threatens women's quality of life,but also has an adverse impact on the entire society economy and family happiness.It is a public health issue of worldwide concern.Although breast cancer has a good prognosis,the five-year survival rate is still different from that of developed countries such as the United States.The 5-year survival rate of patients with early breast cancer can reach more than 90%,indicating that early diagnosis is the key to a better prognosis for breast cancer patients.Breast cancer is a heterogeneous cancer,and both genetic and epigenetic changes contribute to its occurrence and development.However,the underlying molecular and biological functions associated with breast cancer remain unclear.Therefore,we start with epigenetics to explore non-coding RNAs that are differentially expressed in breast cancer,their roles and regulatory mechanisms in breast cancer,and provide potential early clinical screening,diagnosis,and treatment targets for breast cancer diagnosis and treatment.In this study,firstly,we explored the expression of long non-coding RNAs(lncRNA)in breast cancer cells by microarray analysis.The result of microarray analysis and quantitative PCR analysis show a non-coding RNA LncNONHSAT028712(Lnc712)highly expressed in breast cancer cell lines.And the same results were in clinical breast cancer tissue samples.This phenomenon suggests that the expression of Lnc712 may be closely related to the occurrence or development of breast cancer,and may provide early clinical screening for breast cancer.Then,we used specific siRNA interference technology and flow cytometry to find that Lnc712 plays an important role in breast cancer cell proliferation and cell cycle regulation.Similar results were also observed in vivo experiments.In the process of searching for the target of Lnc712,we found that Lnc712 is mainly located in cytoplasm,indicating that Lnc712 may regulate the biological process of cytoplasm,such as binding to cytoplasmic factors,rather than regulating gene expression directly.Subsequent RNA pull down technology confirmed that Lnc712 and Hsp90 formed an RNA-protein complex in the cytoplasm.To further explore the mechanism of Lnc712 combined with Hsp90 to promote breast cancer cell proliferation.We verified the stability of the Lnc712-Hsp90 complex and found that the combination of Lnc712 and Hsp90 may only affect the function of Hsp90.Data suggest that Lnc712 can enhance the interaction between Hsp90 and target protein to inhibit their ubiquitination and degradation.We also found that the expression level of Lnc712 in Adriamycin-resistant MCF-7 cells was higher than that in MCF-7 cells that were Adriamycin-sensitive.fter inhibiting the expression of Lnc712,MCF-7 / ADM cells partially recovered sensitivity to doxorubicin.The data showed that Lnc712 can enhance the ability of breast cancer cells to migrate and the EMT process t was found that a series of effects of Lnc712 in drug-resistant cells were achieved by regulated CDK2.Our results suggest that Lnc712 is high expressed in breast cancer and promotes CDK2 protein folding and maintains the stability of CDK2 in cells by enhancing the interaction between Hsp90 and Cdc37.This promotes the transition of cells from G1 phase to S phase and promotes the process of breast cancer.However,the role of Lnc712 in breast cancer has not been fully understood.The findings in this article only partially revealed the molecular mechanism of Lnc712 in breast cancer proliferation.Therefore,further research is needed to clarify the function of Lnc712 in breast cancer.Lnc712 found in this study regulates breast cancer progression through the Hsp90-Cdc37-CDK2 pathway,providing a new molecular mechanism for clinical treatment of breast cancer.Thus,Lnc712 may be a early screening and promising therapeutic new target in breast cancer.
Keywords/Search Tags:Breast cancer, Long non-coding RNA, Early screening, Therapeutic target
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