Journal ArticleDOI
The circular RNA ciRS-7 (Cdr1as) acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma.
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TLDR
Up-regulated ciRS-7 expression was not only an independent risk factor of hepatic MVI but also had a capable predictive ability for MVI and a novel therapy target for restraining MVI, as suggested by data suggested.Abstract:
Circular RNAs (circRNA) represent a novel class of widespread and diverse endogenous RNAs that regulate gene expression in mammals. microRNA-7 (miR-7) is a well-demonstrated suppressor of hepatocellular carcinoma (HCC). Recent studies have showed that one such circRNA, ciRS-7 (also termed as Cdr1as) was the inhibitor and sponge of miR-7 in the embryonic zebrafish midbrain and islet cells. However, the relationships among ciRS-7, miR-7 and clinical features of HCC remain to be clarified. Expression levels of ciRS-7, miR-7 and three miR-7-targeted mRNAs in 108 pairs of HCC and their matched non-tumor tissues were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The protein production of these three miR-7-targeted mRNAs was further verified by Western blot. The relationship between ciRS-7 level and clinicopathological features as well as the recurrence of HCC patients was analyzed. The univariate and multivariate logistic regression analyses were used to detect the risk factors of hepatic microvascular invasion (MVI). The correlation among ciRS-7, miR-7 and miR-7-targeted mRNAs was evaluated using Spearman’s correlation test. There was no significant difference of ciRS-7 expression levels between the HCC tissues and the matched non-tumor tissues (0.67 ± 1.49 vs. 0.44 ± 0.45, p = 0.13), and the ciRS-7 levels in more than half of HCC tissues (65 out of 108, 60.2 %) were down-regulated when compared with their matched non-tumor tissues. However, the expression of ciRS-7 was significantly correlated with the following three clinicopathological characteristics of HCC patients: age <40 years (p = 0.02), serum AFP ≥400 ng/µl (p < 0.01) and hepatic MVI (p = 0.03). Meanwhile, up-regulated ciRS-7 expression was not only an independent risk factor of hepatic MVI but also had a capable predictive ability for MVI (AUC = 0.68, p = 0.001) at the cut-off value of 0.135. Furthermore, the expression of ciRS-7 in HCC tissues with concurrent MVI was inversely correlated with that of miR-7 (r = −0.39, p = 0.007) and positively related with that of two miR-7-targeted genes [PIK3CD (r = 0.55, p < 0.001) and p70S6K (r = 0.34, p = 0.021)]. In addition, the median recurrent time of patients from higher ciRS-7 level group was shorter than that of lower ciRS-7 group (18 vs. 25 months), but no significant difference was observed (p = 0.38). The expression levels of ciRS-7 were comparable between HCC and matched non-tumor tissues. However, the highly ciRS-7 expression in HCC tissues was significantly correlated with hepatic MVI, AFP level and younger age and thus partly related with the deterioration of HCC. Especially, ciRS-7 was one of the independent factors of hepatic MVI. These data suggested that ciRS-7 may be a promising biomarker of hepatic MVI and a novel therapy target for restraining MVI.read more
Citations
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Journal ArticleDOI
CircRNA: functions and properties of a novel potential biomarker for cancer
Meng Shujuan,Meng Shujuan,Zhou Hecheng,Zhou Hecheng,Feng Ziyang,Feng Ziyang,Xu Zihao,Xu Zihao,Tang Ying,Tang Ying,Peiyao Li,Minghua Wu +11 more
TL;DR: A review of recent research shows that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours.
Journal ArticleDOI
Circular RNAs in cancer: opportunities and challenges in the field.
TL;DR: The current knowledge on circRNAs is reviewed in relation to their implications in tumorigenesis as well as their potential as diagnostic and prognostic biomarkers and as possible therapeutic targets in future personalized medicine.
Journal ArticleDOI
Circular RNAs function as ceRNAs to regulate and control human cancer progression.
Yaxian Zhong,Yaxian Zhong,Yajun Du,Yajun Du,Xue Yang,Xue Yang,Yongzhen Mo,Yongzhen Mo,Chunmei Fan,Fang Xiong,Daixi Ren,Daixi Ren,Xin Ye,Xin Ye,Chunwei Li,Chunwei Li,Yumin Wang,Yumin Wang,Fang Wei,Can Guo,Xu Wu,Xiaoling Li,Xiaoling Li,Yong Li,Yong Li,Guiyuan Li,Guiyuan Li,Zhaoyang Zeng,Zhaoyang Zeng,Wei Xiong,Wei Xiong +30 more
TL;DR: The progress in studying the role of circRNAs as ceRNAs in tumors is reviewed and the participation of circ RNAs in signal transduction pathways to regulate cellular functions is highlighted.
Journal ArticleDOI
Circular RNA and its mechanisms in disease: From the bench to the clinic.
Bing Han,Jie Chao,Honghong Yao +2 more
TL;DR: Although their exact roles and mechanisms of gene regulation remain to be clarified, circRNAs have potential applications as disease biomarkers and novel therapeutic targets.
Journal ArticleDOI
CircRNA: a novel type of biomarker for cancer
TL;DR: Based on the function ofcircRNAs in cancer, it is believed that circRNAs may serve as diagnostic or tumor promising biomarkers and provide a new therapeutic target for the treatment of cancer.
References
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TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Journal ArticleDOI
Natural RNA circles function as efficient microRNA sponges
Thomas B. Hansen,Trine I. Jensen,Bettina Hjelm Clausen,Jesper B. Bramsen,Bente Finsen,Christian Kroun Damgaard,Jørgen Kjems +6 more
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Journal ArticleDOI
Identification of novel genes coding for small expressed RNAs.
TL;DR: It is shown that many 21- and 22-nt expressed RNAs, termed microRNAs, exist in invertebrates and vertebrates and that some of these novel RNAs are highly conserved, which suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by smallRNAs are more general than previously appreciated.
Journal ArticleDOI
Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types
TL;DR: By deep sequencing of RNA from a variety of normal and malignant human cells, this work suggests that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells.