Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells

Wen, Donghua; Xu, Zhijian; Li, Xia; Liu, Xinyi; Tu, Yaoyao; Hu, Lei; Wang, Weiwei; Wang, Tongdan; Song, Lili; Ma, Chunmin; Xu, Hanzhang; Zhu, Weiliang; Chen, Guoqiang; Wu, Yingli

doi:10.1021/pr4012848

Cited by 62 publications

(62 citation statements)

References 40 publications

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“…A sumosylated USP39 has been shown to promote the proliferation of PC-3 and LNcap cells [17]. Nevertheless, the clinical significance of how USP39 is related to PCa has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Huang

Pan

et al. 2016

Oncotarget

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Castration resistance is a serious problem facing clinical treatment of prostate cancer (PCa). The underlying molecular mechanisms of acquired proliferation ability of tumor cells upon androgen deprivation are largely undetermined. In the present study, we identified that ubiquitin specific peptidase 39 (USP39) was significantly upregulated in PCa samples and cell lines. Elevated USP39 expression was positively correlated with Gleason score, predicted a poor outcome, and functioned as an independent risk factor for biochemical recurrence (BCR) especially in patients with a Gleason score ≤7. Our cell-based study showed that the expression level of USP39 was the highest in AR-negative PCa cell lines. Knockdown of USP39 in PCa cells inhibited cancer colony formation and tumor cell growth, and induced G2/M arrest and cell apoptosis. Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR. Silencing of USP39 inhibited the expression of EGFR 3′-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA. Oncomine datasets analysis showed that USP39 expression was positively correlated with EGFR level. The above findings suggest that USP39 plays a vital oncogenic role in the tumorigenesis of PCa and may prove to be a potential biomarker for predicting the prognosis of PCa patients.

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Section: Discussionmentioning

confidence: 99%

“…Wang et al [16] have reported that USP39is overexpressed in breast cancer, and is involved in the tumorigenesis. Wen et al [17] have reported that USP39 is a target of SUMOylation specific protein (SENP) in the proliferation of PCa cells. However, the clinical relevance of USP39 in PCa and its molecular mechanism have rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Huang

Pan

et al. 2016

Oncotarget

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“…However, large-scale experiments and computer predictions suggest that sumoylation [87,88], neddylation [88,89] and ubiquitination [90,91,92,93,94] can occur, and that there may be several kinase target sequences.…”

Section: Synthesis and Fate Of Oat—from Gene To Proteinmentioning

confidence: 99%

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

Ginguay

Cynober

Curis

et al. 2017

Biology

103

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Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme.

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“…For example, the specific acetylation activity pattern of SUMO was shown to alter protein phosphorylation patterns, thus affecting the activity of certain regulatory proteins (35). It has been hypothesized that SENPs modulate the cell cycle and tumorigenesis, utilizing divergent mechanisms (36–38). In the present study, SUMO modification of mRNA expression levels in CAL27 cells differed according to the VPA concentration.…”

Section: Discussionmentioning

confidence: 99%

Anticancer effects of valproic acid on oral squamous cell carcinoma via SUMOylation in vivo and in vitro

Sang

Sun

Ruan

et al. 2016

Experimental and Therapeutic Medicine

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Aberrant histone deacetylase (HDAC) has a key role in the neoplastic process associated with the epigenetic patterns of tumor-related genes. The present study was performed to investigate the effects and determine the mechanism of action of the HDAC inhibitor, valproic acid (VPA), on the CAL27 cell line derived from oral squamous cell carcinoma (OSCC). The effects of VPA on the viability of CAL27 cells were investigated using MTT assays. Alterations in the cell cycle and apoptosis were also examined using propidium iodide (PI) and Annexin V-PI assays, and were subequently analyzed by flow cytometry. Small ubiquitin-related modifier (SUMO)-related genes were evaluated by reverse transcription-quantitative polymerase chain reaction analysis. In addition, the effects of VPA were assessed using a xenograft model in vivo. The present results demonstrated significant dose-dependent inhibition of cell viability following VPA treatment. Treatment with VPA increased the distribution of CAL27 cells in the G1 phase and reduced cells in the S phase, and significantly increased the expression levels of SUMO1 and SUMO2 (P<0.01). Using a xenograft model, the mean tumor volume in VPA-treated animals was demonstrated to be significantly reduced, and the rate of apoptosis was significantly increased, as compared with the control animals. These results suggested that VPA may regulate SUMOylation, producing an anticancer effect in vivo. Further investigation into the role of VPA in tumorigenesis may identify novel therapeutic targets for OSCC.

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Important Role of SUMOylation of Spliceosome Factors in Prostate Cancer Cells

Cited by 62 publications

References 40 publications

Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer via promoting EGFR mRNA maturation and transcription elongation

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

Anticancer effects of valproic acid on oral squamous cell carcinoma via SUMOylation in vivo and in vitro

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