Multilevel regulation and molecular mechanism of poly (rC)‐binding protein 1 in cancer

Zhang, Xuetian; Chen, Di; Chen, Yuhong; Wang, Jing; Su, Ruowei; Huang, Guomin; Xu, Chong; Chen, Xiaohua; Lin, Feng; Yang, Hyejin; Zhang, Hong

doi:10.1096/fj.202000911r

Cited by 17 publications

(14 citation statements)

References 101 publications

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“…It is a novel tumor-suppressive splicing factor that regulates the process of pre-mRNA, mRNA stabilization and translation [ 9 ]. By binding specifically to elements of target mRNAs with AU-rich elements or U-rich elements located in 3’-untranslated regions, PCBP1 regulates diverse gene expression [ 16 ]. Studies showed that PCBP1 protein was significantly downregulated in various primary and metastatic cancers, including gastric cancers [ 17 ], while its mRNA level remained unchanged in most cancer tissues [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1

Lin

Shi

et al. 2022

BMC Cancer

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Background Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of C12orf48 in gastric cancer are largely unknown. Methods We used bioinformatics approaches and tissue microarray immunohistochemistry to analyze the expression profile of C12orf48 in gastric cancer tissues. Plasmid-mediated over-expression or knockdown were performed. CCK-8 assays and flow cytometry were employed to evaluate cellular proliferation and apoptosis respectively. Transwell assays were used to assess migrative and invasive abilities. The roles of C12orf48 were also evaluated in a xenograft tumor model. Results We found that C12orf48 was over-expressed in gastric cancer tissue, which associated with advanced stage and poor prognosis. In vitro and in vivo experiments showed depletion of C12orf48 attenuated cancer growth, while facilitated apoptosis. Further, the expression of Poly r(C)-Binding Protein (PCBP) 1 was found negatively regulated by C12orf48. Intended up-regulation of PCBP1 prevented C12orf48-mediated proliferation and rescued cells from apoptosis. Besides, C12orf48 promoted cellular migration and invasion, with E-cadherin down-regulated while vimentin and N-cadherin up-regulated, which was reversed by up-regulated PCBP1. Conclusions Our findings indicate that depletion of C12orf48 inhibited gastric cancer growth and metastasis via up-regulating PCBP1. Targeting C12orf48-PCBP1 axis may be a potential therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1

Lin

Shi

et al. 2022

BMC Cancer

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“…The decreased CLOCK/BMAL1 transcriptional activity and increased CRY1 repression activity by PCBP1 over-expression (Figure 1E) implied that PCBP1 regulates the core circadian transcription-translation negative feedback loop, which validated our hypothesis. It has been reported that PCBP1 is relevant to tumorigenesis in diverse human cancers (Choi et al, 2009;Shi et al, 2018;Zhang et al, 2020b), and circadian clocks have close interactions with cancer metabolism (Roenneberg and Merrow, 2016;Masri and Sassone-Corsi, 2018). However, the mechanism between these is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of PCBP1 to recognize and bind poly(C) DNA and RNA sequences via KH domains is critical for their function in mammalian cells. As such, PCBP1 binds to various proteins, including iron-containing polyamine pathway dioxygenase ADI1 and signal transducer and activator of transcription 3 (STAT3), and then participates in iron homeostasis, tumorigenesis, and metastasis (Yanatori et al, 2020;Zhang et al, 2020b). Together, these studies describe the complexity of distinct interacting factors that are mediated by PCBP1, which revealed that PCBP1 participate in multiple biological processes.…”

Section: Introductionmentioning

confidence: 99%

Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock

Zhao

Zhang

et al. 2021

Front. Genet.

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The circadian clock governs our daily cycle of behavior and physiology. Previous studies have identified a handful of core clock components and hundreds of circadian modifiers. Here, we report the discovery that poly(C)-binding protein 1 (PCBP1), displaying a circadian expression pattern, was a novel circadian clock regulator. We found that knocking down PCBP1 resulted in period shortening in human U2OS cells, and that manipulations of PCBP1 expression altered the activity of CLOCK/BMAL1 in an E-box-based reporter assay. Further mechanistic study demonstrated that this clock function of PCBP1 appears to work by enhancing the association of Cryptochrome 1 (CRY1) with the CLOCK/BMAL1 complex, thereby negatively regulating the latter’s activation. Co-immunoprecipitation of PCBP1 and core clock molecules confirmed the interactions between PCBP1 and CRY1, and a time-course qPCR assay revealed the rhythmic expression of PCBP1 in mouse hearts in vivo. Given that the RNA interference of mushroom-body expressed (mub), the poly(rC) binding protein (PCBP) homolog of Drosophila, in the clock neurons also led to a circadian phenotype in the locomotor assay, our study deemed PCBP1 a novel clock modifier whose circadian regulatory mechanism is conserved during evolution.

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“…Notably, the antioncogene PCBP1 was reported to be an immune checkpoint required for effector T-cell function, as well as a key molecule in the conversion of the TGF-β signaling pathway from a growth factor inhibitor to a tumor growth promoter in advanced cancer stages (70). PCBP1 was also reported to be associated with the HIF and Akt signaling pathways (82,83). However, the role of miR-490-3p in the regulation of these pathways is yet to be elucidated.…”

Section: Signaling Pathways Associated With Mir-490-3p and Mir-490-5pmentioning

confidence: 99%

MicroRNA‑490‑3p and ‑490‑5p in carcinogenesis: Separate or the same goal? (Review)

Tian

Chen

et al. 2021

Oncol Lett

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MicroRNA (miR)-490-3p and miR-490-5p, located on chromosome 7q33, are two independent mature products of miR-490 exerting distinct effects on tumor progression. miR-490-3p and miR-490-5p possess antitumor properties. miR-490-3p dysfunction has been associated with malignancies including colorectal cancer, while the abnormal function of miR-490-5p has been more considerably associated with bladder cancer (for example). At present, there are 30 and 11 target genes of miR-490-3p and miR-490-5p, respectively, that have been experimentally verified, of which the cyclin D1 (CCND1) gene is a common target. Through these target genes, miR-490-3p and miR-490-5p are involved in 7 and 3 signaling pathways, respectively, of which only 2 are shared regulatory signaling pathways. The present review introduces two competing endogenous RNA (ceRNA) regulatory networks centered on miR-490-3p and miR-490-5p. These networks may be important promoters of tumor cell proliferation, invasiveness, metastatic potential and apoptosis. Unlike miR-490-5p, miR-490-3p plays a unique role in promoting cancer. However, both are promising molecular markers for early cancer diagnosis and prognosis. In addition, miR-490-3p was also found to be associated with the chemical resistance of cisplatin and paclitaxel. The present review focuses on the abnormal expression of miR-490-3p and miR-490-5p in different tumor types, and their complex ceRNA regulatory networks. The clinical value of miR-490-3p and miR-490-5p in cancer diagnosis, prognosis and treatment is also clarified, and an explanation for the opposing effects of miR-490-3p in tumor research is provided.

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Multilevel regulation and molecular mechanism of poly (rC)‐binding protein 1 in cancer

Cited by 17 publications

References 101 publications

Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1

Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1

Identification of PCBP1 as a Novel Modulator of Mammalian Circadian Clock

MicroRNA‑490‑3p and ‑490‑5p in carcinogenesis: Separate or the same goal? (Review)

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