长链非编码TINCR介导乳腺癌化疗耐药的生物信息学分析

Bioinformatics Analysis of Long Non-coding TINCR-mediated Chemotherapy Resistance in Breast Cancer

目的探讨长链非编码RNA-TINCR在耐药性乳腺癌中的表达、生物学功能、相关信号通路及其与患者预后的关系。方法利用GEPIA在线数据库比较人乳腺癌组织和正常组织中TINCR基因的mRNA的相对表达水平,通过qPCR方法验证敏感、耐药乳腺癌细胞中TINCR的表达量,借助Kaplan-Meier ploter在线数据库分析TINCR表达量高低与乳腺癌患者生存预后的关系。采用CCK8法检测改变TINCR表达量对肿瘤细胞化疗敏感性的改变,Metascape在线数据库预测TINCR的相互作用蛋白,借助DAVID对相关基因功能进行GO和KEGG信号通路功能富集分析。最后初步探讨耐药细胞中异常表达的TINCR是如何产生的。结果TINCR在乳腺癌组织及耐药乳腺癌细胞中高表达,升高TINCR表达水平可促进乳腺癌细胞对化疗药物的耐药,分析出TINCR相互作用蛋白有150个,这些蛋白调控蛋白质翻译、mRNA和rRNA的加工、mRNA的出核转运、核糖体小亚基的形成等生物学过程,信号通路富集结果主要分布在核糖体、冠状病毒疾病、剪切体、核质运输、mRNA监测通路等方面。TINCR启动子区具有ERα结合,且使用ERα抑制剂可显著抑制TINCR表达量。结论TINCR在耐药乳腺癌细胞中呈高表达水平,与患者的预后不良有关,对乳腺癌化疗耐药的预测具有重要意义。

Objective To investigate the expression,biological function,signaling pathways and prognosis of long non-coding RNA-TINCR in drug-resistant breast cancer.Methods The GEPIA online database was used to compare the relative expression level of TINCR mRNA in human breast cancer tissues and normal tissues.The expression levels of TINCR in sensitive and resistant breast cancer cells were verified by qPCR method.Kaplan-Meier ploter online database was used to analyze the relationship between TINCR expression level and survival prognosis of breast cancer patients.CCK8 assay was used to detect the change of TINCR expression level on the sensitivity of tumor cells to chemotherapy.The Metascape online database was further used to predict the interacting proteins of TINCR,and the function enrichment analysis of GO and KEGG signaling pathways was conducted with the help of DAVID.Finally,we preliminarily explored how the abnormal expression of TINCR in drug-resistant cells was generated.Results TINCR was highly expressed in breast cancer tissues and drug-resistant breast cancer cells.Elevated TINCR expression level could promote the resistance of breast cancer cells to chemotherapeutic drugs;a total of 150 TINCR-interacting proteins were finally screened.These proteins regulated biological processes such as protein translation,mRNA and rRNA processing,mRNA nuclear export transport,and ribosomal small subunit formation.The results of signal pathway enrichment were mainly distributed in ribosomes,coronavirus diseases,spliceosomes,nucleoplasmic transport,mRNA monitoring pathways,etc.The TINCR promoter region had ERαbinding,and the use of ERαinhibitors could significantly inhibit TINCR expression.Conclusion TINCR is highly expressed in drug-resistant breast cancer cells,which is related to the poor prognosis of patients,and is of great significance for the prediction of chemotherapy resistance in breast cancer.