Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma

Huang, Xiuyan; Huang, Zili; Xu, Yingbin; Zheng, Qi; Chen, Zi; Song, Wei; Zhou, Jian; Tang, Zhao–You; Huang, Xinyu

doi:10.1038/s41598-017-05432-8

Cited by 179 publications

(178 citation statements)

References 54 publications

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“…revealed that the silencing of circ‐MTO1 promoted the in vivo growth of HCC tumor and predicted the poor prognosis in HCC patients . The upregulation of hsa_circ_100338 expression was found to significantly affect the cumulative survival rate and cancer metastasis of HCC patients . In our results, hsa_circ_101280 was upregulated in HCC tissues by microarray analysis and confirmed in HCC tissues and cell lines by qRT‐PCR.…”

Section: Discussionsupporting

confidence: 67%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT‐PCR along with the low expression of its downstream miRNA miR‐375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR‐375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR‐375 by RNA pull‐down and dual‐luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR‐375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR‐375 and upregulating JAK2.

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Section: Discussionsupporting

confidence: 67%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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“…As with other tumors, in HCC, an increasing number of studies has shown that circRNAs are good candidates for miRNA sequestration and the subsequent fine‐tuning of target gene expression . To date, most mechanistic studies of HCC have focused on miRNA sponges.…”

Section: Circrnas and Hccmentioning

confidence: 99%

“…As with other tumors, in HCC, an increasing number of studies has shown that circRNAs are good candidates for miRNA sequestration and the subsequent fine-tuning of target gene expression. 65,66 To date, most mechanistic studies of HCC have focused on miRNA sponges. Huang et al 65 revealed that hsa_circ_0000130 (hsa_circ_100338) functions as an endogenous sponge for miR-141-3p in the regulation of HCC invasion.…”

Section: Circrnas In Hcc Developmental Mechanismsmentioning

confidence: 99%

“…65,66 To date, most mechanistic studies of HCC have focused on miRNA sponges. Huang et al 65 revealed that hsa_circ_0000130 (hsa_circ_100338) functions as an endogenous sponge for miR-141-3p in the regulation of HCC invasion. Through a quantitative proteomics strategy, Yang et al 66 showed that epidermal growth factor receptor (EGFR), a validated miR-7 target, is present in CDR1asoverexpressing HepG2 cells.…”

Section: Circrnas In Hcc Developmental Mechanismsmentioning

confidence: 99%

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Circular RNAs in hepatocellular carcinoma: Functions and implications

Jiang

et al. 2018

Cancer Medicine

108

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At present, as hotspot members of the noncoding RNA network, circular RNAs (circRNAs) with distinct properties and diverse pathophysiological functions are being increasingly delineated. CircRNAs play roles at the epigenetic, transcriptional and posttranscriptional regulatory levels. Major studies have focused on their functions as efficient microRNA sponges. The validated number of endogenous circRNAs involved in hepatocellular carcinoma (HCC) continues to increase. Altered circRNA expression is associated with HCC occurrence, invasion, and metastasis. Moreover, the aberrant expression of circRNAs is also significantly related to HCC tumor stage, size, differentiation and metastasis. Because they are exceptionally stable, highly conserved and have tissue‐specific expression patterns, some circRNAs, including hsa_circ_0004018, hsa_circ_0003570, and hsa_circ_0005075, may be potential markers for the diagnosis of HCC. We herein summarize the current knowledge of HCC‐associated circRNAs and present their implications for carcinogenesis and their potential value as diagnostic and prognostic biomarkers. Finally, we discuss the future directions of studies on HCC‐associated circRNAs.

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“…Shang et al showed that hsa_circ_0005075 could be used to diagnose HCC. Huang et al discovered that circRNA‐100338 could serve as a prognostic indicator for HCC. KOU et al demonstrated that hsa_circ_0078602 expression level was linked to prognosis among patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma

et al. 2019

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Circular RNAs (circRNAs) have been increasingly revealed to be desirable biomarkers for some tumors, including hepatocellular carcinoma (HCC). Combined with our previous microarray screening results, we aimed to determine the hsa_circ_0028502 and hsa_circ_0076251 expression features in HCC, analyze the relationship between their expression level and clinical and pathological characteristics, and investigate their diagnostic and prognostic values. Our data demonstrated that the hsa_circ_0028502 and hsa_circ_0076251 levels were considerably lower in HCC tissues than in adjacent paracancerous tissues (P < .001). Further study revealed that hsa_circ_0028502 expression levels were related to tumor node metastasis (TNM) stage (P = .015) and that hsa_circ_0076251 expression levels were related to Barcelona Clinic Liver Cancer (BCLC) stage (P = .038), comorbidity with type 2 diabetes mellitus (P = .023) and the presence of serum HbsAg (P = .044). Furthermore, the degree of expression of both hsa_circ_0028502 and hsa_circ_0076251 increased from HCC to liver cirrhosis (LC) to chronic hepatitis (CH). The receiver operating characteristic (ROC) curve demonstrated that hsa_circ_0028502 and hsa_circ_0076251 could serve as fairly accurate markers to distinguish HCC tissues from CH tissues and LC tissues, as well as distinguishing LC tissues from CH tissues. Cox regression analysis showed that low expression of has_circ_0076251 was associated with unfavorable survival rates in HCC (HR = 0.46; 95% CI = 0.22‐0.98; P < .05). These findings implied that hsa_circ_0028502 and hsa_circ_0076251 were potentially valuable biomarkers for HCC diagnosis, whereas hsa_circ_0076251 could be used as a prognostic indicator for HCC.

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Comprehensive circular RNA profiling reveals the regulatory role of the circRNA-100338/miR-141-3p pathway in hepatitis B-related hepatocellular carcinoma

Cited by 179 publications

References 54 publications

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Circular RNAs in hepatocellular carcinoma: Functions and implications

Hsa_circ_0028502 and hsa_circ_0076251 are potential novel biomarkers for hepatocellular carcinoma

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