Abstract
The etiology of cancer includes aberrant cellular homeostasis where a compromised RNA regulatory network is a prominent contributing factor. In particular, noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were recently shown to play important roles in the initiation, progression, and metastasis of human cancers. Nonetheless, a mechanistic understanding of noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA) database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151 lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by targeting interrelations with significantly aberrant expression data between miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1, MIR31HG, and MIR99AHG) significantly correlated with survival (P < 0.05). Finally, real-time quantitative PCR analysis showed that PLAU is significantly upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our findings represent new knowledge for a better understanding the ceRNA network in LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.
Highlights
Lung cancer is the most prevalent cancer worldwide, being the top cause of cancer-related deaths in the world, including China (Chen et al, 2016)
We found 3,564 mRNAs to be differentially expressed between the early-stage group and control group, 3,864 mRNAs were differentially expressed between the mid-stage group and control group, and 3,818 mRNAs were differentially expressed between the late-stage group and control group (Fig. 1A)
Cancer-specific miRNAs and long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LUSC) and their competitive endogenous RNA (ceRNA) network We identified the miRNAs and lncRNAs differentially expressed between the LUSC tumor tissues and the adjacent non-tumorous tissues from the the updated Cancer Genome Atlas (TCGA) database
Summary
Lung cancer is the most prevalent cancer worldwide, being the top cause of cancer-related deaths in the world, including China (Chen et al, 2016). LUSC is highly malignant and accounts for over 400,000 new cases worldwide each year (Gandara et al, 2015). It still has a poor cure rate, with the 5-year survival rate among patients with clinical LUSC stages II to IV ranging from 40% to less than 5% (Tanoue & Detterbeck, 2009). This situation is largely due to a lack of knowledge about its molecular pathogenesis, and for this reason, little effective targeted therapy for LUSC is currently approved
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