LncRNA HULC promotes non-small cell lung cancer cell proliferation and inhibits the apoptosis by up-regulating sphingosine kinase 1 (SPHK1) and its downstream PI3K/Akt pathway

摘要

OBJECTIVE: LncRNA HULC has been proved to have important functions in the pathogenesis of several types of cancers. While its involvement in non-small cell lung cancer (NSCLC), which is one of the most common malignancies, still hasn’t been reported to date. Therefore, we aimed to investigate the role of HULC in NSCLC and to explore the possible mechanisms. PATIENTS AND METHODS: Tumor tissues and adjacent healthy tissues were collected from NSCLC patients, and blood samples were collected from both NSCLC patients and healthy controls. Expression of HULU in those tissues was detected by qRT-PCR. All patients were followed up for 5 years. Diagnostic and prognostic values of serum HULU for NSCLC were investigated by ROC curve analysis and survival curve analysis, respectively. HULC overexpression NSCLC cell lines were established and its effects on cell proliferation as well as apoptosis were investigated by CCK-8 assay and MTT assay, respectively. Effects of HULC overexpression on sphingosine kinase 1 (SPHK1) and its downstream PI3K/Akt pathway were investigated by Western blot. RESULTS: HULC expression level was increased in tumor tissues compared with adjacent healthy tissues in most patients. Serum level of HULC was higher in cancer patients than that in healthy control. Serum level of HULC was increased with the increased stage of primary tumor (T stage). Serum HULC can be used to accurately predict NSCLC and its prognosis. HULC overexpression promoted tumor cell proliferation, but inhibited cell apoptosis. HULC overexpression also increased expression level of SPHK1 and phosphorylation level of Akt in NSCLC cell, but showed on significant effects on Akt expression. Treatment with SPHK1 inhibitor and Akt reduced the effects of HULC overexpression on proliferation and apoptosis of NSCLC cells. But the treatment showed no significant effects on HULC expression. SPHK1 inhibitor treatment inhibited phosphorylation of Akt, while Akt inhibitor treatment showed no significant effects on SPHK1 expression. CONCLUSIONS: LncRNA HULC overexpression can promote NSCLC cell proliferation and inhibit cell apoptosis by up-regulating sphingosine kinase 1 (SPHK1) and further induce the activation of its downstream PI3K/Akt pathway.