Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

Adhikary, Jayashree; Chakraborty, Sourabrata; Dalal, Subhamita; Basu, Souradip; Dey, Abhijit; Ghosh, Amlan

doi:10.1136/jclinpath-2019-205891

Cited by 40 publications

(27 citation statements)

References 73 publications

(74 reference statements)

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“…19 Up to now, the oncogenic role of circPVT1 has been confirmed in several human tumors, including OS. 23,30 There is only one report involved in the effects of circPVT1 on tumor cell metastasis, and whether this effect is mediated by EMT remains undetermined. 20 In our study, circPVT1 was found highly expressed in OS tissues and cell lines, which is consistent with the conclusion of the previous study.…”

Section: Discussionmentioning

confidence: 99%

circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma

Liu

Wan

Lin

et al. 2020

CMAR

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Background: As a key subtype of non-coding RNAs, circular RNA (circRNA) has been well documented to play a key role in the tumorigenesis of osteosarcoma (OS). circPVT1 was revealed to participate in the progression of multiple human tumors; however, the roles of circPVT1 in OS invasion and metastasis and its potential mechanisms remain elusive. Methods: RNA expression in OS tissues and cells was examined by qRT-PCR, protein expression was measured by Western blot. circPVT1 knockdown in vitro was achieved by transfecting OS cells with specific siRNAs. OS cell proliferation was assessed via CCK-8 and colony formation assays. OS cell migration and invasion were evaluated by transwell assay. Interaction between miR-205-5p and circPVT1 or c-FLIP was validated through dualluciferase reporter assay. Rescue experiments were performed to explore the regulatory net among circPVT1, miR-205-5p and c-FLIP in OS progression in vitro. Results: circPVT1 and c-FLIP were highly expressed, while miR-205-5p was lowly expressed in OS tissues and cell lines. Knockdown of circPVT1 repressed cell proliferation, migration and invasion via inhibiting epithelial-mesenchymal transition (EMT) in OS. circPVT1 functioned as a sponge of miR-205-5p, and c-FLIP was targeted by miR-205-5p in OS cells. Furthermore, circPVT1 indirectly regulated c-FLIP expression through competitively binding to miR-205-5p. Inhibition of miR-205-5p or overexpression of c-FLIP abolished the effects of si-circPVT1 on cell proliferation, migration and invasion. Conclusion: Our study demonstrated circPVT1 functions as a sponge for miR-205-5p to promote c-FLIP expression, thereby enhancing EMT and inducing OS invasion and metastasis in vitro, implying that circPVT1 might be a potential therapeutic target for further clinical therapy of OS.

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Section: Discussionmentioning

confidence: 99%

circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma

Liu

Wan

Lin

et al. 2020

CMAR

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“…5 PVT1 gene displayed frequent amplification at genome level and concordant transcriptional up-regulation in different malignancies. 6,7 Increasing evidence has revealed the carcinogenic effects of PVT1 on various tumors, such as non-small-cell lung cancer, hepatocellular cancer, leukemia, ovarian and breast cancer. [8][9][10][11] In CRC, several studies suggested that PVT1 functioned as an oncogene to promote CRC tumorigenesis through regulating cell biological behavior.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis

Liu¹,

Wu²,

Guan³

et al. 2020

CMAR

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Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear. Methods: The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 (FJX1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or FJX1 was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model. Results: PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted FJX1, and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1 up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1 expression via targeting miR-106b-5p. Conclusion: Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1 axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.

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“…The biological consequences of PVT1 and circPVT1 alterations are often attributed to the downstream deregulation of MYC. Evidence obtained across hematological malignancies indicates that the regulatory role exerted on cell proliferation by PVT1 (in AML, T-ALL, BL, MM) and circPVT1 (in T-ALL, B-ALL) is mediated by MYC, as also observed in a number of solid tumors [95,96], and this regulation is active at post-transcriptional level (Fig. 3).…”

Section: Pvt1 and Circpvt1: Myc Partners In Crime And Beyondmentioning

confidence: 68%

Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin

et al. 2020

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Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.

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Circular PVT1: an oncogenic non-coding RNA with emerging clinical importance

Cited by 40 publications

References 73 publications

<p>circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma</p>

<p>circPVT1 Facilitates Invasion and Metastasis by Regulating miR-205-5p/c-FLIP Axis in Osteosarcoma</p>

<p>Knockdown of PVT1 Suppresses Colorectal Cancer Progression by Regulating MiR-106b-5p/FJX1 Axis</p>

Linear and circular PVT1 in hematological malignancies and immune response: two faces of the same coin

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