Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. However, there is a shortage of suitable diagnostic markers for early stages of NSCLC, and therapeutic targets are limited. Right open reading frame (Rio) kinase 2 (RIOK2) and Nin one binding (NOB1) protein are important accessory factors in ribosome assembly and are highly expressed in malignant tumours; moreover, they interact with each other. However, the RIOK2 expression profile and its clinical significance as well as NOB1’s mechanism in NSCLC remain unknown. In this study, NSCLC cell lines and 15 NSCLC tumour tissues (paired with adjacent normal lung tissues) were collected for a real-time quantitative PCR (RT-qPCR) analysis. In addition, 153 NSCLC cases and 27 normal lung tissues were used in an immunohistochemical analysis to evaluate the RIOK2 and NOB1 expression profiles, their clinicopathological factors in NSCLC and their correlations with prognoses. RIOK2 and NOB1 were highly expressed in NSCLC cells and tissues, and their expression profiles were significantly associated with the Tumour Node Metastasis (TNM) clinical stage, lymph node metastasis, and differentiation. RIOK2 expression was correlated with NOB1. The results suggested that simultaneously determining the expression of RIOK2 and NOB1 will improve the diagnostic rate in early stages of NSCLC. Moreover, RIOK2 and NOB1 might be potential targets for NSCLC therapy.
Highlights
Lung cancer is the most common global cancer and the second leading cause of cancer death
The RIO family of proteins includes RIOK1, RIOK2 and RIOK3, which have the characteristics of kinases but lack a typical kinase domain; they are referred to as atypical kinases[14]
RIOK1 and RIOK2 are highly conserved in eukaryotes including yeast and mammals, and RIOK3 is expressed in only eukaryotic cells[14,26]
Summary
Lung cancer is the most common global cancer and the second leading cause of cancer death. The nin one binding (NOB1) protein has recently been found to be highly expressed in several cancers, and it plays a significant role in tumourigenesis. Our previous studies have shown that abnormal NOB1 expression is related to lung cancer, especially NSCLC; NOB1 is significantly highly expressed in NSCLC patients, and this expression is associated with the TNM stage, lymph node metastasis and histopathological grade[12,13]. RIO molecules are highly expressed in many tumours[20,21,22,23,24]; previous studies have not evaluated the relationship between RIOK2 and NSCLC. We investigated the expression of both RIOK2 and NOB1 in the same NSCLC patients. We further assessed the clinicopathological significance of RIOK2 and NOB1 and the prognostic value of the relationship between these proteins
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