Chemotherapeutic insensitivity remains one of the major obstacles in clinical treatment of lung squamous cell carcinoma (LSCC). Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) promote tumorigenesis in many cancer types. However, the potential biological roles and regulatory mechanisms of lncRNAs in response to cisplatin treatment are poorly understood. Here, we found that lncRNA SFTA1P (surfactant associated 1, pseudogene), highly expressed in lung, was down-regulated in LSCC tissues and could be induced upon cisplatin treatment in LSCC cells. Elevated SFTA1P induced apoptosis and enhanced the sensitivity to cisplatin of LSCC cells. We further identified that hnRNP-U (heterogeneous nuclear ribonucleoprotein U) was down-regulated in LSCCs and positively correlated with patients' poor prognosis as well as SFTA1P. Mechanistic studies revealed that SFTA1P could up-regulate hnRNP-U expression. In addition, we identified that hnRNP-U enhanced cisplatin-induced apoptosis through up-regulation of GADD45A, high expression of which was correlated with good prognosis in LSCC patients. Our findings demonstrated that SFTA1P might serve as a useful biomarker for LSCC diagnosis and a predictor for cisplatin chemotherapy response in patients with LSCC.
Keywords: apoptosis; cisplatin chemosensitivity; hnRNP-U- GADD45A; long noncoding RNA SFTA1P; lung squamous cell carcinoma.