A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma

Zhang, Maolei; Zhao, Kun; Xu, Xiaoping; Yang, Yibing; Yan, Sheng; Wei, Ping; Liu, Hui; Xu, Jianbo; Xiao, Feizhe; Zhou, Huangkai; Yang, Xuesong; Huang, Nunu; Liu, Jinglei; He, Kejun; Xie, Keping; Zhang, Gong; Huang, Suyun; Zhang, Nu

doi:10.1038/s41467-018-06862-2

Cited by 546 publications

(464 citation statements)

References 63 publications

(68 reference statements)

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“…In addition, circRNAs have also been reported to be a type of promising biomarker . Currently, circRNAs have attracted more attention as they have been reported to alter the aggressive phenotypes of different human cancers . For example, circ_ciRS‐7‐a facilitated cell‐cycle, and might be a promising biomarker in colorectal cancer .…”

Section: Discussionmentioning

confidence: 99%

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Circular RNA 0007255 regulates the progression of breast cancer through miR‐335‐5p/SIX2 axis

Jia

et al. 2020

Thoracic Cancer

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Background Breast cancer (BC) is a common cancer in women worldwide. Emerging evidence has indicated that circular RNA hsa‐circ_0007255 (circ_0007255) is a prognostic mediator in BC progression. However, the functional role of circ_0007255 needs to be determined. Methods The expression of circ_0007255, microRNA (miR)‐335‐5p, and SIX Homeobox 2 (SIX2) was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot assay. Actinomycin D and RNase R treatment was performed to analyze the stability of circ_0007255. Additionally, Seahorse extracellular flux, colony formation and transwell analyses were carried out to detect oxygen consumption ratio (OCR), colony formation and cell mobility, respectively. The interaction between miR‐335‐5p and circ_0007255 or SIX2 was confirmed via dual‐luciferase reporter assay. A xenograft tumor model was established to explore the role of circ_0007255 in vivo. Results Circ_0007255 and SIX2 were overexpressed, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 absence inhibited oxygen consumption, colony formation, cell migration and invasion, and these effects were particularly abrogated via miR‐335‐5p upregulation in BC cells. Moreover, SIX2 deficiency eliminated the promotion effects of miR‐335‐5p inhibitor on oxygen consumption, colony formation, and cell mobility in BC cells. Importantly, circ_0007255 inhibited tumor growth in vivo. Mechanically, circ_0007255 was a sponge of miR‐335‐5p to regulate SIX2 expression in BC progression. Conclusion Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment. Key points Significant findings of the study: Levels of circ_0007255 and SIX2 were upregulated, but miR‐335‐5p was diminished in BC tissues and cells. Circ_0007255 was an oncogene in BC development and exerted its function via miR‐335‐5p/SIX2 axis in BC. Tumor growth was reduced by circ_0007255 absence. What this study adds: Circ_0007255 functioned as a novel oncogene in the progression of BC by regulating miR‐335‐5p/SIX2 axis, and might be a promising biomarker for BC treatment.

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Section: Discussionmentioning

confidence: 99%

“…27 Currently, circRNAs have attracted more attention as they have been reported to alter the aggressive phenotypes of different human cancers. [28][29][30] For example, circ_ciRS-7-a facilitated cell-cycle, and might be a promising biomarker in colorectal cancer. 28 However, the role of circRNAs in BC still requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA 0007255 regulates the progression of breast cancer through miR‐335‐5p/SIX2 axis

Jia

et al. 2020

Thoracic Cancer

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“…For example, In gastric cancer, LINC‐PINT is decreased and it can predict the poor survival . In glioblastoma, a peptide, which is encoded by LINC‐PINT represses the oncogenic transcriptional elongation . In acute lymphoblastic leukemia, deregulation of LINC‐PINT participates in the abnormal proliferation of leukemic cells .…”

Section: Discussionmentioning

confidence: 99%

“…24 In glioblastoma, a peptide, which is encoded by LINC-PINT represses the oncogenic transcriptional elongation. 25 In acute lymphoblastic leukemia, deregulation of LINC-PINT participates in the abnormal proliferation of leukemic cells. 26 In addition, LINC-PINT can function as a tumor inhibitor through sponging miR-543 and miR-576-5p in esophageal cancer.…”

Section: Linc-pint Inhibited Lung Cancer Cell Tumorigenicity In Vivomentioning

confidence: 99%

LINC‐PINT alleviates lung cancer progression via sponging miR‐543 and inducing PTEN

et al. 2020

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Long intergenic nonprotein coding RNA p53‐induced transcript (LINC‐PINT) has been reported to participate in various cancers. Here, we investigated the effects of LINC‐PINT on lung cancer progression. Firstly, in our study, we implied that LINC‐PINT was obviously decreased in NSCLC. Thereafter, in A549 and H1299 cells, LINC‐PINT was upregulated via transfecting LV‐LINC‐PINT. As exhibited, LINC‐PINT repressed cell proliferation and cell colony formation of A549 and H1299 cells. Subsequently, flow cytometry evidenced that A549 and H1299 cell apoptosis was obviously triggered and the cell cycle was arrested in G1 phase. Then, migration and transwell invasion experiments were carried out to detect the cell migration and invasion capacity. We found A549 and H1299 cell migration and invasion capacity were restrained by the upregulation of LINC‐PINT. Meanwhile, we predicted that miR‐543 could function as the target of LINC‐PINT and the association was verified. Moreover, we exhibited that miR‐543 was remarkably increased in lung cancer, which could be regulated by LINC‐PINT negatively. Furthermore, PTEN could act as the downstream target of miR‐543 and upregulation of miR‐543 repressed PTEN, which was reversed by LV‐PINT in A549 and H1299 cells. Finally, xenografts were utilized to confirm the function of LINC‐PINT on lung cancer. All these findings concluded that LINC‐PINT exerted crucial biological roles in NSCLC through sponging miR‐543 and inducing PTEN.

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“…Additionally, synthetic circRNAs have been engineered to express protein by the use of internal ribosome entry sites (IRESs) allowing cap-independent translation (Wang and Wang 2015). Recently, it was shown that open reading frames (ORFs) within endogenously expressed circRNAs give rise to circRNA-specific peptides (Legnini et al 2017; Pamudurti et al 2017; Yang et al 2017; Zhang et al 2018a; Yang et al 2018; Zhang et al 2018b) suggesting that circRNAs are not necessarily exclusively non-coding.…”

Section: Introductionmentioning

confidence: 99%

Non-coding AUG circRNAs constitute an abundant and conserved subclass of circles

Stagsted

Nielsen

Daugaard

2018

Preprint

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A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma

Cited by 546 publications

References 63 publications

Circular RNA 0007255 regulates the progression of breast cancer through miR‐335‐5p/SIX2 axis

Circular RNA 0007255 regulates the progression of breast cancer through miR‐335‐5p/SIX2 axis

LINC‐PINT alleviates lung cancer progression via sponging miR‐543 and inducing PTEN

Non-coding AUG circRNAs constitute an abundant and conserved subclass of circles

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