NONO and tumorigenesis: More than splicing

Feng, Peifu; Li, Ling; Deng, Tanggang; Liu, Yan; Ling, Neng; Qiu, Siyuan; Zhang, Lin; Peng, Bo; Wang, Xiong; Cao, Lei; Zhang, Lei; Ye, Mao

doi:10.1111/jcmm.15141

Cited by 50 publications

(44 citation statements)

References 108 publications

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“…With roles in almost every step of gene regulation, it is not surprising that abnormal expression of NONO results in malignant transformation of normal cells. To date, emerging evidences have demonstrated that NONO was frequently overexpressed in various cancer and is an independent prognostic factor for some cancers [ 11 ]. Although NONO is functionally characterized and has profound impact on tumorigenesis in a spectrum of cancer types, only few has been fully characterized.…”

Section: Discussionmentioning

confidence: 99%

“…And DBHS proteins are frequently identified engaging in almost every step of gene regulation, including but not limited to transcriptional regulation and RNA processing [ 10 ]. A total of 54 kDa nuclear RNA- and DNA-binding protein/Non-POU-domain-containing octamer binding protein (p54 nrb /NONO), one member of DBHS family, dysregulated in many types of cancers [ 11 ]. Our previous work demonstrated that NONO was upregulated in breast cancer and stimulated lipogenesis by interacting with and stabilizing sterol regulatory element-binding protein 1 (SREBP1) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Nuclear scaffold protein p54nrb/NONO facilitates the hypoxia-enhanced progression of hepatocellular carcinoma

et al. 2021

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Hypoxia and related oxidative stress are closely related to the development and treatment of hepatocellular carcinoma (HCC). However, the mechanism mediated by hypoxia in HCC has not yet been elucidated. Here, we found multifunction scaffold protein p54nrb/NONO exerted pleiotropic effects to regulate hypoxia transcription signals, thereby enhancing the progression of liver cancer. Extensive analysis of clinical data demonstrated that NONO was significantly upregulated and represented as a poor prognostic indicator of HCC. The crucial role of NONO in driving angiogenesis and glycolysis, two well-known cancer phenotypes mediated by hypoxia, was examined in vitro an in vivo. Mechanistically, NONO interacted with and stabilized both HIF-1 and HIF-2 complexes thus activating the transcription of hypoxia-induced genes. Besides, NONO bound pre-mRNA and subsequent mRNA of these genes to facilitate them splicing and mRNA stability, respectively. Thus, NONO knockout seriously disrupted the expression of a cluster of HIF-1/2 targets and impeded hypoxia-enhanced progression in HCC. In conclusion, NONO functioned as a multipurpose scaffold that interacted with HIF-1/2 complex and their downstream transcripts to facilitate the expression of hypoxia-induced genes, allowing malignant proliferation, indicating that NONO might be a potential therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear scaffold protein p54nrb/NONO facilitates the hypoxia-enhanced progression of hepatocellular carcinoma

et al. 2021

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“…Non-POU domain-containing octamer-binding protein (NONO), also known as 54-kDa nuclear RNA-and DNAbinding protein (p54 nrb ), belongs to the Drosophila behavior/human splicing family and functions in a variety of physiologic processes including mRNA splicing [8], transcriptional regulation [9], DNA repair [10], and nuclear retention of defective RNA [11]. NONO also plays an important role in the regulation of malignant phenotypes in cancer cells [12]. In breast cancer, NONO increased nuclear sterol regulatory element-binding protein (SREBP)−1a protein stability and stimulated SREBP-1a-mediated transcription of lipogenic genes and lipid production, thus promoting breast cancer growth [13].…”

Section: Introductionmentioning

confidence: 99%

PRMT1 enhances oncogenic arginine methylation of NONO in colorectal cancer

Yin

Wang

et al. 2021

Oncogene

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Arginine methylation is an important posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs). However, the role of PRMTs in colorectal cancer (CRC) progression is not well understood. Here we report that non-POU domain-containing octamer-binding protein (NONO) is overexpressed in CRC tissue and is a potential marker for poor prognosis in CRC patients. NONO silencing resulted in decreased proliferation, migration, and invasion of CRC cells, whereas overexpression had the opposite effect. In a xenograft model, tumors derived from NONO-deficient CRC cells were smaller than those derived from wild-type (WT) cells, and PRMT1 inhibition blocked CRC xenograft progression. A mass spectrometry analysis indicated that NONO is a substrate of PRMT1. R251 of NONO was asymmetrically dimethylated by PRMT1 in vitro and in vivo. Compared to NONO WT cells, NONO R251K mutant-expressing CRC cells showed reduced proliferation, migration, and invasion, and PRMT1 knockdown or pharmacological inhibition abrogated the malignant phenotype associated with NONO asymmetric dimethylation in both KRAS WT and mutant CRC cells. Compared to adjacent normal tissue, PRMT1 was highly expressed in the CRC zone in clinical specimens, which was correlated with poor overall survival in patients with locally advanced CRC. These results demonstrate that PRMT1-mediated methylation of NONO at R251 promotes CRC growth and metastasis, and suggest that PRMT1 inhibition may be an effective therapeutic strategy for CRC treatment regardless of KRAS mutation status.

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“…RNA binding proteins (RBPs) have recently emerged as critical factors that regulate multiple cellular activities, including pre-mRNA splicing, translation and protein sub-cellular localization ( 29 , 30 ). NONO is a novel RBP that is located in the nucleus of numerous mammalian cells and distributed in the sub-nuclear domain and participates in almost every step of gene regulation ( 31 ). Studies have found that NONO also serves an important role in tumorigenesis, including proliferation regulation, DNA damage repair, cell migration and apoptosis ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis

Qin

Tong

et al. 2021

Int J Mol Med

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Sphingosine-1-phosphate (S1P) serves an important role in various physiological and pathophysiological processes, including the regulation of cell apoptosis, proliferation and survival. Sphingosine kinase 1 (SPHK1) is a lipid kinase that phosphorylates sphingosine to generate S1P. S1P has been proven to be positively correlated with chemotherapy resistance in breast cancer, colorectal carcinoma and non-small cell lung cancer. However, whether SPHK1 is involved in the development of cisplatin resistance remains to be elucidated. The present study aimed to identify the association between SPHK1 and chemoresistance in bladder cancer cells and to explore the therapeutic implications in patients with bladder cancer. Bladder cancer cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. Apoptosis-related proteins were detected via western blotting. The results revealed that SPHK1 was positively correlated with cisplatin resistance in bladder cancer cells, exhibiting an antiapoptotic effect that was reflected by the downregulation of apoptosis-related proteins (Bax and cleaved caspase-3) and the upregulation of an antiapoptotic protein (Bcl-2) in SPHK1-overexpression cell lines. Suppression of SPHK1 by small interfering RNA or FTY-720 significantly reversed the antiapoptotic effect. A potential mechanism underlying SPHK1-induced cisplatin resistance and apoptosis inhibition may be activation of STAT3 via binding non-POU domain containing octamer binding. In conclusion, the present study suggested that SPHK1 displayed significant antiapoptotic effects in cisplatin-based treatment, thus may serve as a potential novel therapeutic target for the treatment for bladder cancer.

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NONO and tumorigenesis: More than splicing

Cited by 50 publications

References 108 publications

Nuclear scaffold protein p54nrb/NONO facilitates the hypoxia-enhanced progression of hepatocellular carcinoma

Nuclear scaffold protein p54nrb/NONO facilitates the hypoxia-enhanced progression of hepatocellular carcinoma

PRMT1 enhances oncogenic arginine methylation of NONO in colorectal cancer

SPHK1 contributes to cisplatin resistance in bladder cancer cells via the NONO/STAT3 axis

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