Upregulated hsa_circ_0004458 Contributes to Progression of Papillary Thyroid Carcinoma by Inhibition of miR-885-5p and Activation of RAC1

Jin, Xiaoyan; Wang, Zhengyi; Pang, Wenyang; Zhou, Jian; Liang, Yong; Yang, Jingjin; Yang, Linjun; Zhang, Qiang

doi:10.12659/msm.911095

Cited by 43 publications

(34 citation statements)

References 41 publications

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“…Fig 3A displays a diagram of the 29 exon-containing linear PSD3 mRNA and circPSD3 that is derived from a back-splicing event between exons 5 and 8 [ 43 ]. Four siRNAs overlapping the exon5/8 junction sequences depleted to various extents circPSD3 RNAs ( Fig 3B ), with only small effects on the abundances of linear PSD3 mRNAs ( Fig 3C ).…”

Section: Resultsmentioning

confidence: 99%

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Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells

et al. 2020

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Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro-and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed proviral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus-and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.

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Section: Resultsmentioning

confidence: 99%

“… ( A ) Diagram of the linear PSD3 RNA and circPSD3 that is generated by a backsplicing event between exons 5 and 8 [ 43 ]. ( B-D ) Effects of depletion of circPSD3 RNA by four different siRNAs, which all target the back-spliced junction site in circPSD3 RNA.…”

Section: Resultsmentioning

confidence: 99%

Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells

et al. 2020

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“…Figure 3A displays a diagram of the 29 exon-containing linear PSD3 mRNA and circPSD3 that is derived from a back-splicing event between exons 5 and 8 [43]. Four siRNAs overlapping the exon5/8 junction sequences depleted to various extents circPSD3 RNAs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…( A ) Diagram of the linear PSD3 RNA and circPSD3 that is generated by a backsplicing event between exons 5 and 8 [43]. ( B-D ) Effects of depletion of circPSD3 RNA with four different siRNAs, which all target the back-spliced junction site in circPSD3 RNA on ( B ) circPSD3 RNA, ( C ) linear PSD3 RNA and ( D ) HCV RNA abundances were determined by using RT-qPCR.…”

Section: Resultsmentioning

confidence: 99%

Host-derived Circular RNAs Display Proviral Activities in Hepatitis C Virus - Infected Cells

Chen

Talló-Parra

Kadener

et al. 2020

Preprint

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2930 Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification 31 or to counteract innate immune responses. Roles for host-encoded RNAs, including 32 microRNAs, have been found to provide pro-and anti-viral functions. Recently, circular RNAs 33 (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have 34 been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA 35 landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the 36 abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected 37 cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, 38 circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C 39 virus-and Dengue virus-infected cells. Surprisingly, circPSD3 also inhibited the cellular 40 nonsense-mediated decay (NMD) pathway in liver cells. Thus, enhanced abundance of 41 circPSD3 in virus-infected cells aids in viral replication and likely contributes to the known 42 inhibition of NMD in HCV-infected cells. Findings from the global analyses of the circular RNA 43 landscape argue pro-, and likely, anti-viral functions are executed by circRNAs that modulate 44 both viral gene expression as well as host pathways. Because of their long half-lives, circRNAs 45 likely play hitherto unknown, important roles in viral pathogenesis. 46 47 48 Author Summary 49 50 Usually, cells are infected by one or a few virus particles that carry genomes with limited 51 expression capacity. Thus, the expression of viral genomes has to compete with a sea of 52 cellular components that aid in viral translation, replication and virion production. Depending on 53 their lifestyle, viruses have evolved to avoid or to subvert cellular pathways, especially those 3 54 that display anti-viral functions. Host-derived circular RNA molecules have recently been 55 discovered in the cytoplasm of cells, although, as-of yet, few functions have been assigned to 56 them. Here, we describe alterations in the circular RNA landscape in hepatitis C virus-infected 57 liver cells. Up-regulated and down-regulated circular RNAs were identified, and three of the 58 upregulated RNAs were shown to promote HCV infection. One of them, circPSD3, inhibited the 59 cellular nonsense-mediated RNA decay that is a powerful antiviral response in infected cells. 60 Because circular RNAs are more stable than linear RNAs, they may have important functions 61 during viral infection, dictating the outcomes of innate immune responses and viral 62 pathogenesis. 63 64 Introduction 65 66 Cicrular RNAs (circRNAs) were first detected in plant viral RNA pathogens, termed viroids [1].67 Subsequently, it has shown that eukaryotic cells express circRNAs as well [2, 3]. Some 68 circRNAs contain scrambled exons, which are produced by an abnormal splicing mechanism 69 [4]. Recently, it has been shown that circRNA species are synthesized from pre-...

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“…Circ_0025033 was elevated in PTC and promoted PTC cell growth and metastasis and inhibited apoptosis via sponging miR-1231 and miR-1304 [26]. Jin et al disclosed that circ_0004458 was elevated in PTC and silencing of circ_0004458 hampered cell growth and facilitated apoptosis and cell cycle arrest in PTC cells in vitro and restrained tumorigenesis in vivo [27]. These findings all indicated the oncogenic role of circRNAs in PTC.…”

Section: Discussionmentioning

confidence: 97%

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

Gui

Zhang

et al. 2020

Cancer Cell Int

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Background: Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we aimed to explore the effects of circ_LDLR on PTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were conducted to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to determine cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_ LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo. Results: Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_ LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. Conclusion: Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.

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Upregulated hsa_circ_0004458 Contributes to Progression of Papillary Thyroid Carcinoma by Inhibition of miR-885-5p and Activation of RAC1

Cited by 43 publications

References 41 publications

Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells

Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells

Host-derived Circular RNAs Display Proviral Activities in Hepatitis C Virus - Infected Cells

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

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