Silencing of the long non-coding RNA 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. 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 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts.

RESULTS

We found that high levels of expression were associated with shorter overall survival rate of patients, whereas knockdown of inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of induced autophagy and apoptosis. Moreover, we showed that 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 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.

CONCLUSIONS

Our findings thus identify SIN3A as a -associated protein and should help to understand the mechanism underlying -mediated oncogenesis.