Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

Yao, Renzhi; Zou, Haifan; Liao, Weijia

doi:10.3389/fonc.2018.00332

Cited by 59 publications

(59 citation statements)

References 143 publications

(190 reference statements)

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“…Compared with linear RNA, circRNAs are more stable, abundant, conserved due to its special circular structure. 4 , 5 Recently, studies have demonstrated that a novel circRNA, circMAT2B, can contribute to cell proliferation, thereby promoting the growth of hepatocellular carcinoma (HCC). 6 However, the precise mechanisms of circMAT2B-induced CRC cell proliferation are unknown.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression

Zhao

Chen

2020

CMAR

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Purpose: Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood. Materials and Methods: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression. Results: In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih. gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=−0.5131, p<0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation. Conclusion: circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

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Section: Introductionmentioning

confidence: 99%

Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression

Zhao

Chen

2020

CMAR

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“…21 What is important, circRNAs are also potential molecules, functioning in the diagnosis, therapy, and prognosis of patients with HCC. 22 It is a fact that numerous circRNAs often exhibit cell type-specific, tissue-specific or developmental stage-specific expression. 23 , 24 Situated at chromosome X: 139865339-139866824, circ_CDR1as (also named as hsa_circ_0001946 or ciRS-7), is a risk factor for HCC; Besides, circ_CDR1as is downregulated in HCC cells and tissues, affecting physiological function of HCC cells by targeting miR-7 and regulating EGFR signaling.…”

Section: Discussionmentioning

confidence: 99%

CircRNA CDR1as/miR-1287/Raf1 Axis Modulates Hepatocellular Carcinoma Progression Through MEK/ERK Pathway

Zhang¹,

Li²,

Zhu³

et al. 2020

CMAR

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Background: Hepatocellular carcinoma (HCC) is a common lethal malignant tumor worldwide. Circular RNAs (circRNAs) have been reported to affect the development of human cancers, including HCC. In this project, we aim to clarify the functional effect of circular CDR1as (circ_CDR1as) on HCC progression. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot is implemented to detect the expression of circ_CDR1as, microRNA (miR)-1287 and Raf-1 proto-oncogene, serine/threonine kinase (Raf1). Cell proliferation is assessed via colony formation and 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assays. Cell migration and invasion are measured by Transwell assay. The target relationship between miR-1287 and circ_CDR1as or Raf1 is validated through dual-luciferase reporter assay. The levels of epithelia-mesenchymal transition (EMT) markers and the MEK/ERK signal pathway-related proteins are examined by Western blot. Model in nude mice is constructed to determine the role of circ_CDR1as in vivo. Results: Expression of circ_CDR1as and Raf1 is elevated, while miR-1287 expression is decreased in HCC. Depletion of circ_CDR1as or Raf1 could inhibit proliferation and metastasis of HCC cells. Besides, circ_CDR1as regulates Raf1 expression by targeting miR-1287. MiR-1287 upregulation or Raf1 depletion could partially counterbalance circ_CDR1as depletion-mediated inhibitory effects on HCC cell behaviors. Moreover, circ_CDR1as depletion represses HCC progression through inactivating MEK/ERK pathway. In addition, circ_CDR1as depletion suppresses tumor growth in vivo via regulating miR-1287/Raf1 pathway. Conclusion: Circ_CDR1as depletion inhibits HCC cell proliferation and metastasis by miR-1287/Raf1 and MEK/ERK pathways, highlighting a promising molecular target for HCC treatment.

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“…137 Overall, circRNAs played key roles in tumorigenesis and development, epigenetic regulation, drug resistance, and could be considered as immune-associated biomarker and therapeutic target in HCC. [138][139][140][141][142][143][144] Regardless, more in-depth study of circRNA biofunctions in HCC is greatly desired.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Biological Roles and Mechanisms of Circular RNA in Human Cancers

Tang

Hann

2020

OTT

136

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Circular RNA (circRNA) is an intriguing class of RNA with covalently closedloop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

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Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker and Therapeutic Target

Cited by 59 publications

References 143 publications

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

<p>CircRNA CDR1as/miR-1287/Raf1 Axis Modulates Hepatocellular Carcinoma Progression Through MEK/ERK Pathway</p>

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

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