PUF60 accelerates the progression of breast cancer through down-regulation of PTEN expression

Sun, Dongying; Lei, Wei; Hou, Xiaodong; Li, Hui; Ni, Wenlu

doi:10.2147/cmar.s180242

Cited by 26 publications

(25 citation statements)

References 33 publications

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“…PUF60 is essential, and heterozygous loss of function causes Verheij syndrome, which is characterized by severe developmental abnormalities in most patients ( Low et al, 2017 ; Verheij et al, 2009 ). PUF60 is also involved in Hepatitis B virus infection ( Sun et al, 2017 ) and cancer progression ( Sun et al, 2019 ). In C. elegans , we found a G281D amino acid substitution in rnp-6 lying within the second RNA binding motif at a position conserved across evolution ( Figure 1D ).…”

Section: Resultsmentioning

confidence: 99%

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Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60

Kew

Huang

Fischer

et al. 2020

eLife

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Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in C. elegans, we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner, and rnp-6 gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/PMK-1/MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.

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Section: Resultsmentioning

confidence: 99%

“…Because PUF60 is involved in various human diseases ( Sun et al, 2019 ; Sun et al, 2017 ; Xu et al, 2018 ), we next explored the potential role of rnp-6 in imparting immunity in higher organisms. We first asked if PUF60, the mammalian homolog of rnp-6 , is regulated during infection.…”

Section: Resultsmentioning

confidence: 99%

Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60

Kew

Huang

Fischer

et al. 2020

eLife

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“…Poly-U binding splicing factor 60 kDa (PUF60), a factor regulating RNA splicing, is closely involved in tumor progression. The expression of PUF60 was highly correlated with TNM staging and lymph node metastasis in breast cancer (Sun et al, 2019b). Kobayashi et al (2016) detected PUF60 auto-antibodies in the sera of early-stage colon cancer patients and concluded that it may be a candidate biomarker for the diagnosis and prognosis of colon cancer.…”

Section: Discussionmentioning

confidence: 97%

Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis

Guo

Wang

Sun

et al. 2020

PeerJ

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Purpose Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma that is incurable with standard therapies. The use of gene expression analysis has been of interest, recently, to detect biomarkers for cancer. There is a great need for systemic coexpression network analysis of MCL and this study aims to establish a gene coexpression network to forecast key genes related to the pathogenesis and prognosis of MCL. Methods The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database. We systematically identified coexpression modules using the weighted gene coexpression network analysis method (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were performed on the modules deemed important. The protein–protein interaction networks were constructed and visualized using Cytoscape software on the basis of the STRING website; the hub genes in the top weighted network were identified. Survival data were analyzed using the Kaplan–Meier method and were compared using the log-rank test. Results Seven coexpression modules consisting of different genes were applied to 5,000 genes in the 121 human MCL samples using WGCNA software. GO and KEGG enrichment analysis identified the blue module as one of the most important modules; the most critical pathways identified were the ribosome, oxidative phosphorylation and proteasome pathways. The hub genes in the top weighted network were regarded as real hub genes (IL2RB, CD3D, RPL26L1, POLR2K, KIF11, CDC20, CCNB1, CCNA2, PUF60, SNRNP70, AKT1 and PRPF40A). Survival analysis revealed that seven genes (KIF11, CDC20, CCNB1, CCNA2, PRPF40A, CD3D and PUF60) were associated with overall survival time (p < 0.05). Conclusions The blue module may play a vital role in the pathogenesis of MCL. Five real hub genes (KIF11, CDC20, CCNB1, CCNA2 and PUF60) were identified as potential prognostic biomarkers as well as therapeutic targets with clinical utility for MCL.

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“…Furthermore, we demonstrated that PUF60 could promote RCC cell growth through mediating TERT signaling in vitro and in vivo. It has been reported that PUF60 has tumor promoting effects in breast cancer [49], but it remains to be investigated whether this effect of PUF60 depends on TERT signaling. According to our experimental data in Fig.…”

Section: Discussionmentioning

confidence: 99%

Poly(U) binding splicing factor 60 promotes renal cell carcinoma growth by transcriptionally upregulating telomerase reverse transcriptase

Qian

Hua

et al. 2020

Int. J. Biol. Sci.

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Background: Abnormal transcriptional upregulation of telomerase reverse transcriptase (TERT) plays a dominant role in telomerase activation in various cancers. TERT promoter mutations (TPMs) have been identified as a key mechanism in TERT upregulation. However, the mechanism of TERT upregulation in cancers with low frequency of TPMs are not fully elucidated so far. Methods: The expression of PUF60 and TERT was detected by real-time PCR, western blot and immunohistochemistry. TERT promoter binding proteins were identified by streptavidin-agarose pulldown assay and mass spectrum (MS) analysis. The role of PUF60/TERT in renal cancer was evaluated on cell growth in vitro and in vivo. Results: In this study, we identify the regulation mechanism of TERT in renal cell carcinoma (RCC) cells which have rare TPMs but exert significant upregulation of TERT. We found that TERT was highly expressed in RCC tumor tissues, and elevated TERT expression was associated with poor prognosis for patients. We also detected the relatively rare TPM status in both RCC tumor tissues and RCC cell lines. Mechanistically, PUF60, a RNA binding protein, was identified as a novel TERT regulator which bound to the TERT and transcriptionally upregulated TERT expression in RCC cells. The in vitro and in vivo experiments also demonstrated that PUF60 could promote RCC cell growth through activation of TERT expression in a TPM status independent way. Furthermore, we showed that there was a strong correlation of the expression of PUF60 and TERT in RCC tumor tissues and RCC cell lines, and the patients with high expression of PUF60 and TERT had significantly shorter survival. Conclusions: Collectively, these results indicated that PUF60 transcriptionally upregulated TERT expression to promote RCC growth and progression in a TPM status independent way, suggesting that the PUF60/TERT signaling pathway may serve as potential prognostic biomarkers and therapeutic targets for RCC.

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PUF60 accelerates the progression of breast cancer through down-regulation of PTEN expression

Cited by 26 publications

References 33 publications

Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60

Evolutionarily conserved regulation of immunity by the splicing factor RNP-6/PUF60

Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis

Poly(U) binding splicing factor 60 promotes renal cell carcinoma growth by transcriptionally upregulating telomerase reverse transcriptase

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