Role of TELO2-interacting protein 1(TTI1) functions as an oncogene by regulating mTOR activity in the progression of non-small cell lung cancer

Abstract

Background: The role of TTI1 in the progression of several types of cancer has been reported recently. The aim of this study was to estimate the expression and the potential value of TTI1 in non-small cell lung cancer (NSCLC) patients.Methods: The expression of TTI1 and its prognostic value in NSCLC from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were analyzed. To verify the bioinformatics findings, a tissue microarrays (TMAs) containing 160 NSCLC and paired peritumoral tissues from NSCLC patients was analysed by immunohistochemistry for TTI1. Subsequently, the roles of TTI1 in NSCLC cells were investigated in vivo by establishing xenograft models in nude mice, and in vitro by transwell, CCK-8 assay, wound healing and colony formation assays. In addition, qRT-PCR and western blot were applied to explore the underlying mechanism by which TTI1 promotes tumor progression. Finally, the relation between TTI1 and KI67 expression level of NSCLC was probed, and Kaplan-Meier and Cox's analyses were performed to assess the prognostic merit of TTI1 and KI67 in NSCLC patients. Results: The expression of TTI1 was significantly upregulated in NSCLC tissues compared to paired peritumoral tissues, which was coincide with the bioinformatics findings from TCGA and GEO database. TTI1 was highly expressed in NSCLC patients with large tumor, advanced tumor stage, and lymphatic metastasis. In addition, the prognostic analysis identified the TTI1 as an independent indication for poor prognosis of NSCLC patients. In vitro, Up-regulation of TTI1 in NSCLC cells could facilitate cell invasion, metastasis, viability and proliferation. Mechanistically, our study verified that TTI1 could regulate mTOR activity which has a pivotal role in human cancer. Consistently, the TTI1 and KI67 expression had a positive relationship in NSCLC cells and tissues. Notably, compared with patients with low expression of TTI1 or KI67, patients with overexpression of TTI1 or KI67 had a shorter overall survival rate (OS) and a higher disease-free survival rate (DFS), and the combination of TTI1 and KI67 was an independent parameter predicting the prognosis and recurrence of NSCLC patients. Conclusions: TTI1 promotes NSCLC cell proliferation, metastasis and invasion by regulating mTOR activity and the combination of TTI1 and KI67 is a valuable molecular biomarker for the survival and recurrence of NSCLC patients.