Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene

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.

Mechanism of vascular endothelial growth factor on the prevention of restenosis after angioplasty

To evaluate the mechanism of vascular endothelial growth factor(VEGF)on the prevention of restenosis after angioplasty,the recombinant adenovirus vector containing hVEGF165 cDNA was constructed and transfected into vascular smooth muscle cells(VSMC)in vitro.The conditioned medium containing VEGF was collected 72 h after the infection.Then,the VSMC and human umbilical vein endothelial cells(HUVEC)were divided into control group,H2O2-treated group and H2O2+VEGF-treated group to observe the proliferation and apoptosis by water soluble tetrazolium(WST-1)method,in situ nick end labeling(TUNEL)andflow cytometry(FCM).Compared with the control and H2O2+VEGF-treated groups,the absorbance(A)value of HUVEC was decreased,and apoptosis of HUVEC was significantly increased in H2O2-treated group.The changes of A value and apoptosis of VSMC were contrary to those of HUVEC.H2O2 could stimulate the proliferation of VSMC and induce the apoptosis of HUVEC,inhibit the proliferation of HUVEC and the apoptosis of VSMC and induce restenosis.VEGF could inhibit the effect of H2O2 on HUVEC and VSMC and prevent restenosis.These results offered further theoretical evidence for VEGF on the prevention of restenosis after angioplasty.