Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upreg...Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer.However,the mechanism underlying its function in cancer progression remains poorly understood.Methods:Here,the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines,clinical samples,and xenografts.Results:We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients,whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts.Western blot andflow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis.Moreover,we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a(SIN3A),which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner.Silencing of SIN3A also reduced proliferation of lung cancer cells,which was correlated with the induction of autophagy.These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.Conclusions:Ourfindings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.展开更多
基金supported in part by the National Natural Science Foundation of China(NSFC)(82073388 to SWM)the Natural Outstanding Youth Fund of Guangdong Province(2022B1515020090 to SWM)+1 种基金Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases(2022B1212030003 to SWM)the Affiliated Hospital of Guangdong Medical University Clinical Research Program(LCYJ2020B005 to SWM).
文摘Background:Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes.Their dysregulation has been closely associated with tumorigenesis.LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer.However,the mechanism underlying its function in cancer progression remains poorly understood.Methods:Here,the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines,clinical samples,and xenografts.Results:We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients,whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts.Western blot andflow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis.Moreover,we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a(SIN3A),which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner.Silencing of SIN3A also reduced proliferation of lung cancer cells,which was correlated with the induction of autophagy.These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.Conclusions:Ourfindings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.
