DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF‑κB pathway

Abstract

DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry. The percentage of DKC1 expression in ccRCC (61.3%) was markedly higher than that in paracancerous tissues (34.7%) (P=0.001). Positive DKC1 expression tends to significantly be associated with unfavorable clinicopathological characteristics such as tumor diameter >7 cm (P=0.002) and tumor‑node‑metastasis (TNM) stage III or IV (P<0.001). Multivariate COX analysis revealed that positive DKC1 expression was an independent unfavorable factor for prognosis of ccRCC patients [hazard ratio (HR)=1.932, 95% CI, 1.290‑2.893, P=0.001 for 5‑year overall survival; HR=1.778, 95% CI,1.150‑2.748, P=0.010 for disease‑free survival]. In the PROGgeneV2 platform, we also found that ccRCC patients with high DKC1 mRNA expression had a poorer prognosis than patients with low DKC1 expression in The Cancer Genome Atlas (TCGA). Furthermore, we found that knockdown of DKC1 inhibited proliferation, migration and invasion of ccRCC through regulation of the NF‑κB/MMP‑2 signaling pathway in vitro. We also demonstrated that DKC1 regulated ccRCC proliferation and the expression of NF‑κB‑p65 and MMP‑2 in vivo. In summary, the expression of DKC1 was upregulated in ccRCC, which was associated with unfavorable clinicopathological characteristics and DKC1 may act as an independent prognostic indicator of ccRCC patients.

The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer

“…The current study confirms the significant association between the high expression of DKC1, at both protein and mRNA levels, and clinicopathological parameters characteristics of poor prognosis and with shorter survival; findings which are in-line with other studies. 15 , 44 , 45 Some studies have also confirmed that DKC1 overexpression is involved in tumorigenic processes and has prognostic value in numerous types of cancer. 19 , 21 , 46 The association between DKC1 mRNA and shorter survival was identified in both METABRIC and TCGA cohorts.…”

Bioinformatics Analysis Reveals Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma

“…DKC1 is highly expressed in clear cell renal cell carcinoma. DKC1 knockout inhibits tumor proliferation, migration, and invasion by regulating the NF-κB/MMP-2 signaling pathway in vitro (Zhang M. et al, 2018).…”

H/ACA snoRNP Gene Family as Diagnostic and Prognostic Biomarkers for Hepatocellular Carcinoma

“…Cui et al 21 suggested that loss of NOP10 may inhibit lung cancer cell growth, colony formation, migration, and invasion indicating that NOP10 has an oncogenic role in NSCLC. Zhang et al 22 suggested that the expression of DKC1 in clear cell renal cell carcinoma (ccRCC) was markedly higher than that in adjacent tissues, and knockdown of DKC1 inhibited ccRCC progression through the NF-κB/MMP-2 signaling pathway. Another study by Elsharawy et al 23 indicated that the overexpression of DKC1 contributes to the proliferation and progression of aggressive breast cancer.…”