Recent studies have demonstrated the importance of non-protein coding part of human genome in carcinogenesis and metastasis. Among numerous kinds of non-protein coding RNAs, long noncoding RNAs (lncRNAs) play a key regulatory role in cancer biology. LncRNAs are dysregulated in different kinds of cancer and the expression levels of certain lncRNAs are associated with recurrence, metastasis, and prognosis of cancer. It is also proved that overexpression of certain lncRNAs, behaving like oncogenes, can promote matrix invasion of cancer cells and tumor growth. In this review, we focus our attention on lncRNAs those have been validated in human cancer tissues to suggest reasonable strategies for future research. We introduce an update view of lncRNA, extract cancer-related lncRNAs from literature, and describe the known functions and possible underlying molecular mechanisms of some well investigated lncRNAs (MALAT1, HOX antisense intergenic RNA, and highly upregulated in hepatocellular cancer), as well as their current and potential future application in cancer diagnosis (PCA3) and treatment (H19).
1Somatic copy-number variations (CNV) may drive cancer progression through both coding and 2 noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, 3 especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and 4 focal CNV in lung adenocarcinoma (LAC), we identify a proto-oncogenic circular RNA 5 (circPRKCI) from the 3q26.2 amplicon, one of the most frequent genomic aberrations in multiple 6 cancers. circPRKCI was overexpressed in LAC tissues, in part due to amplification of the 3q26.2 7 locus, and promoted proliferation and tumorigenesis of LAC. circPRKCI functioned as a sponge 8 for both miR-545 and miR-589 and abrogated their suppression of the pro-tumorigenic 9 transcription factor E2F7. Intra-tumor injection of cholesterol-conjugated siRNA specifically 10 targeting circPRKCI inhibited tumor growth in a patient-derived LAC xenograft model. In 11 summary, circPRKCI is crucial for tumorigenesis and may serve as a potential therapeutic target in 12 LAC patients. 13
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly types of cancer worldwide especially in Eastern Asia and the prognosis of ESCC remain poor. Recent evidence suggests that circular RNAs (circRNAs) play important roles in multiple diseases, including cancer. In this study, we characterized a novel circRNA termed hsa_circ_0067934 in ESCC tumor tissues and cell lines. We analyzed a cohort of 51 patients and found that hsa_circ_0067934 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues. The high expression level of hsa_circ_0067934 was associated with poor differentiation (P = 0.025), I-II T stage (P = 0.04), and I-II TNM stage (P = 0.021). The in vitro silence of hsa_circ_0067934 by siRNA inhibited the proliferation and migration of ESCC cells and blocked cell cycle progression. Cell fraction analyses and fluorescence in situ hybridization detected that hsa_circ_0067934 was mostly located in the cytoplasm. Our findings suggest that hsa_circ_0067934 is upregulated in ESCC tumor tissue. Our data suggest that hsa_circ_0067934 represents a novel potential biomarker and therapeutic target of ESCC.
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