Emerging landscape of circular RNAs in lung cancer

Hu, Wei; Bi, Zhuoyue; Chen, Zhenlong; Liu, Cong; Li, Linlin; Zhang, Feng; Zhou, Qun; Zhu, Wei; Song, Yan; Zhan, Bo-Tao; Zhang, Qian; Bi, Yang; Sun, Chengcao; Li, Dejia

doi:10.1016/j.canlet.2018.04.006

Cited by 101 publications

(77 citation statements)

References 100 publications

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“…circRNAs will be more sensitive and specific as cancer biomarkers for diagnosis and therapy than antigen–antibody reactions. Thus, hsa_circ_101280 can be used as an HCC biomarker and can be detected by qRT‐PCR and in situ hybridization . In addition, several circRNAs have been confirmed to act as miRNA sponges and to be involved in circRNA‐miRNA‐mRNA axis .…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…Thus, hsa_circ_101280 can be used as an HCC biomarker and can be detected by qRT-PCR and in situ hybridization. 35,36 In addition, several circRNAs have been confirmed to act as miRNA sponges and to be involved in circRNA-miRNA-mRNA axis. 37 For instance, circ-SRY functioned as a sponge of miR-138 in colorectal and ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Cao

Wang

et al. 2018

Immunol Cell Biol

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“…Circular RNAs (circRNAs) are a new class of abundant endogenous functional non-coding RNAs (ncRNAs), and have been demonstrated to play important roles in different types of cancer, including gastric cancer, lung cancer, and HCC [2][3][4]. They form covalently closed continuous loop structures with neither polarity nor polyadenylated tails, which make them more stable and abundant than their canonical linear transcripts from the same genes in cells [5,6].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA Signature in Hepatocellular Carcinoma

Qiu¹,

Wang²,

Ge³

et al. 2019

J. Cancer

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Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Circular RNAs (circRNAs) are a new class of endogenous functional non-coding RNAs (ncRNAs), and have been demonstrated to play important roles in the development of HCC. This study aimed to explore the significance of circRNAs in HCC progression. HCC-associated circRNA expression profiles GSE94508 and GSE97332 were downloaded from the Gene Expression Omnibus database (GEO), and 87 differentially expressed circRNAs (DECs) between HCC tissues and paired non-cancer tissues were identified, including 76 up-regulated and 11 down-regulated circRNAs. Gene ontolog (GO) and pathway analyses of the host genes of these DECs suggested that these host genes were enriched in cell adhesion, cytosol, and protein binding, and were associated with tight junction and Wnt signaling pathways. CircRNA-miRNA interaction prediction identified 20 miRNAs that predispose to interact with DECs. Among these, four essential miRNAs, hsa-miR-7-5p, hsa-miR-145-5p, hsa-miR-203a-3p, and hsa-miR-192-5p, were reported to play pivotal roles in HCC progression by targeting multiple genes. Pathway analysis suggested that putative target genes of these essential miRNAs were involved in HCC-associated signaling pathways, such as Wnt, TGF-β, and Ras; whereas protein-protein network (PPI) analysis demonstrated that some validated target genes of these miRNAs, such as PIK3CA, AKT1, MYC, JUN, SMAD4, and SRC, were hub target genes as they have more counts of interacting protein. In the meantime, the deregulation of some DECs was validated in HCC cell line HepG2 compared with normal liver cell line L02 by quantitative real-time polymerase chain reaction (qRT-PCR) and the Sanger sequencing. This study identified a set of DECs in HCC, and provided a comprehensive understanding of the roles of these DECs in HCC progression.

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“…Due to their closed structure, circRNAs are stable and resistant to RNA degradative pathways; circRNAs therefore show promise as novel molecular markers in various diseases, including cancer, myocardial infarction, diabetes, and cerebral infarction . The circRNAs function importantly in tumor progression and carcinogenesis in NSCLC . The circRNA hsa_circ_0014130 (circPIP5K1A) was identified as a novel biomarker that is highly overexpressed in tissues of NSCLC comparing with adjacent tissues .…”

Section: Introductionmentioning

confidence: 99%

“…11 The circRNAs function importantly in tumor progression and carcinogenesis in NSCLC. [12][13][14] The circRNA hsa_circ_0014130 (circPIP5-K1A) was identified as a novel biomarker that is highly overexpressed in tissues of NSCLC comparing with adjacent tissues. 15 However, the underlying regulatory mechanism remains unclear.…”

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confidence: 99%

Circular RNA circPIP5K1A promotes non‐small cell lung cancer proliferation and metastasis through miR‐600/HIF‐1α regulation

Chi

Luo

Song

et al. 2019

J of Cellular Biochemistry

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Circular RNAs (circRNAs) have an important function in human diseases, especially in cancer. circRNA hsa_circ_0014130 (circPIP5K1A), a particularly abundant circRNA, participates in the tumorigenesis of non‐small cell lung cancer (NSCLC), although the underlying regulatory mechanism remains unclear. Here, we investigated the circPIP5K1A role in NSCLC. Expression of circPIP5K1A in NSCLC cell lines was explored with quantitative real‐time PCR. The effect of circPIP5K1A on NSCLC was evaluated with circPIP5K1A silencing, miR‐600 mimic transfection, and hypoxia‐inducible factor (HIF)‐1α overexpression, followed by assessment of cell proliferation, metastasis, and tumorigenesis in nude mice. The subcellular localization of circPIP5K1A was evaluated via fluorescence in situ hybridization (FISH), and correlation between circPIP5K1A, miR‐600, and HIF‐1α was assessed by luciferase assay. The data demonstrated that circPIP5K1A expression was increased in NSCLC cells. FISH showed that circPIP5K1A localized to the cytoplasm. The circPIP5K1A knockdown suppressed NSCLC cell metastasis and proliferation by promoting expression of miR‐600. Overexpression of miR‐600 inhibited HIF‐1α‐mediated metastasis and proliferation of NSCLC cell by downregulating the endothelial mesenchymal transition‐related proteins, Snail and vimentin, and upregulating E‐cadherin. In vivo experiments illustrated that circPIP5K1A silence suppressed tumor growth and pulmonary metastasis. The circPIP5K1A may function as an miR‐600 sponge to facilitate NSCLC proliferation and metastasis by promoting HIF‐1α. A bifluorescein reporter experiment confirmed that miR‐600 was the circPIP5K1A target, and miR‐600 interacted with the 3′ untranslated region of HIF‐1α. These results show that circPIP5K1A acted as a tumor promoter through a novel circPIP5K1A/miR‐600/HIF‐1α axis, which provides candidate markers and therapeutic targets for NSCLC.

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Emerging landscape of circular RNAs in lung cancer

Cited by 101 publications

References 100 publications

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR‐375/JAK2

Circular RNA Signature in Hepatocellular Carcinoma

Circular RNA circPIP5K1A promotes non‐small cell lung cancer proliferation and metastasis through miR‐600/HIF‐1α regulation

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