Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 (SNORA42) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907, in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.

Genomic analysis of high-risk smoldering multiple myeloma

“…21 For example, SNORA42 has been shown to act as a potential oncogene in the development and progression of lung cancer. 22 Furthermore, homozygous and heterozygous deletions in U50, a C/D snoRNA, have been described in prostate and breast cancer tissues, respectively. 23,24 On the other hand, there are some preliminary data showing that the genes that host snoRNAs might also contribute to cancer pathogenesis.…”

Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies

“…snoRNA are non-coding RNAs (ncRNA) that are less well known than other ncRNAs, such as miRNAs and siRNAs, that could be actively involved in the development of cancer. [44][45][46][47] In this setting, global downregulation is a characteristic feature of snoRNAs in cancer cells. For example, it has been recently reported that leukemic cells show infraexpression of several snoRNAs.…”

Specific small nucleolar RNA expression profiles in acute leukemia

“…3 Recent new cellular functions have led us to hypothesize that snoRNA accumulation patterns could be modulated in cancer. [10][11][12]14,[30][31][32][33][34][35] Acute leukemia is a good model to try to answer this question as it is characterized by restrictive oncogenic events leading to a blockade in differentiation.…”