<scp>USP</scp>33 mediates <scp>S</scp>lit‐<scp>R</scp>obo signaling in inhibiting colorectal cancer cell migration

Huang, Zhaohui; Wen, Pushuai; Kong, Ruirui; Cheng, Haipeng; Zhang, Bin-Bin; Cao, Qing; Bian, Zehua; Chen, Mengmeng; Zhang, Zhenfeng; Chen, Xiaoping; Du, Xiang; Liu, Jianghong; Zhu, Li; Fushimi, Kazuo; Hua, Dong; Wu, Jane Y.

doi:10.1002/ijc.29226

Cited by 54 publications

(58 citation statements)

References 39 publications

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“…The role of Slit-Robo and its functions in cancer treatment and development are becoming increasingly unraveled but also increasingly complex. Consistent with in colorectal cancer and breast cancer [18, 19], our results showed that USP33 can function by interacting with Robo1 in PTC cells, which may enhancing the Slit-Robo signaling and thus inhibit tumor progression. Furthermore, our data suggested that USP33 can activate caspase 9 and caspase 3 proteins, in accordance with the fact that Robo1 functions partly by inducing cell apoptosis [26].…”

Section: Discussionsupporting

confidence: 72%

USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma

Meng

Guo

2018

Cell Physiol Biochem

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Background/Aims: To investigate the clinical significance and functional mechanisms of deubiquitinase USP33 in papillary thyroid carcinoma (PTC). Methods: Immunohistochemistry staining was conducted to explore the expression of USP33 in PTC tissues and adjacent normal thyroid tissues. Patients’ prognosis was evaluated by disease-free survival. The prognostic role of USP33 was tested by univariate and multivariate analyses. To confirm the effect of USP33 in cell proliferation and invasion, overexpression and knockdown of USP33 were performed in two PTC cell lines. Besides, cell cycle, immunoprecipitation, and apoptosis experiments were conducted to further explore the signaling pathways. Results: By analyzing series of 158 PTC tissues, we found that USP33 was down-regulated in tumor tissue compared with normal thyroid tissues, which was closely associated with lymph node metastasis (P<0.001). In particular, univariate and multivariate analyses indicated that USP33 was an independent prognostic biomarker for PTC, low USP33 expression indicated high recurrence risk. Cellular studies with TPC-1 and BCPAP cells demonstrated that USP33 can attenuate the cell capacities of proliferation, migration and invasion. Fluorescence-activated cell sorting experiment found no significant effect of USP33 on cell cycle, whereas the apoptotic caspase proteins were activated by USP33-overexpression. Moreover, the interaction between USP33 and Robo1 protein was identified, and knockdown of Robo1 enhancing the oncogenic effect upon USP33-knockdown, suggesting that USP33 may inhibit tumor progression through Robo1 signaling. Conclusions: Our data demonstrated that USP33 downregulation in PTC tissues was correlated with poor clinical outcome, which may serve as a novel biomarker and potential therapeutic target.

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Section: Discussionsupporting

confidence: 72%

USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma

Meng

Guo

2018

Cell Physiol Biochem

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“…Although the importance of some members of the USP family in a variety of biological processes [29], such as regulation of DNA damage checkpoint response, epigenetic regulation and protein stabilization is well established, very little is known about the biological function of the majority of the USPs. Here, we revealed that USP47 is a direct target of miR-204-5p in GC and knockdown USP47 expression could Fig.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A

Zhang

Yin

et al. 2014

Med Oncol

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MicroRNAs (miRNAs) are a type of small noncoding RNAs that are strongly implicated in carcinogenesis. However, the potential diagnostic, prognostic and therapeutic roles of the majority of miRNAs in the pathological processes of tumorigenesis remain largely unknown. Our and others' data revealed that miR-204-5p was significantly downregulated in gastrointestinal tumor tissues compared with adjacent noncancerous tissues. The downregulation of miR-204-5p was confirmed in our gastric cancer (GC) cohort, and we showed that ectopic expression of miR-204-5p inhibited, whereas silencing miR-204-5p expression promoted GC cell proliferation in vitro. Subsequent mechanistic investigations identified that USP47 and RAB22A are direct functional targets of miR-204-5p in GC. Silencing the expression of USP47 and RAB22A using siRNA phenocopied the proliferation-inhibiting function of miR-204-5p in GC cells. Our results uncovered that miR-204-5p acts as a tumor suppressor in GC through inhibiting USP47 and RAB22A.

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“…The functional significance of USP33 has been investigated in breast, colon and lung cancer cells. USP33 can inhibit the migration of these cells by its deubiquitinating activity on Robo [38][39][40]. Here, we found that USP33 could deubiquitinate and stabilize PPM1A (Fig.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andmentioning

confidence: 64%

Radiation Enhances the Epithelial– Mesenchymal Transition of A549 Cells via miR3591-5p/USP33/PPM1A

Zhong

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Radiotherapy plays a critical role in lung cancer treatment. Radiation can activate transforming growth factor-β (TGF-β) signaling and induce the epithelial-mesenchymal transition (EMT), which may lead to distant metastases. MicroRNAs (miRNAs) have been suggested to affect radiotherapy in lung cancer. Methods: miRNA Next-Generation Sequencing was performed to investigate the effects of irradiation on the miRNA profile of lung cancer A549 cells. The functions of identified miRNA on the radiation induced EMT and TGF-β activation in A549 cells were then explored. Protein expression was evaluated by western blotting. Immunofluorescence staining was performed to detect the localization of Snail. Luciferase Assay was used to determine the target gene regulated by the identified miRNA. Results: Radiation time-dependently induced EMT in A549 lung cancer cells as indicated by the changes of morphology, the expression of EMT marker proteins (E-cadherin, α-SMA and Vimentin) and the nuclear localization of Snail. Moreover, miR-3591-5p was identified as the most significant increased miRNA in response to radiation, and further experiments indicated that miR-3591-5p was required for radiation induced EMT and TGF-β/ Smad2/3 activation. Ubiquitin Specific Peptidase 33 (USP33) was a downstream target of miR-3591-5p as predicted by TargetScan and validated by 3’ untranslated regions (UTRs) Luciferase Assay. USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2+/Mn2 + dependent 1A), a phosphatase for Smad2/3. Ectopic expression of USP33 or PPM1A partially abolished the effects of miR-3591-5p on EMT and TGF-β/ Smad2/3 activation. Conclusion: The present study revealed the critical role of miR-3591-5p/USP33/PPM1A in radiation-induced EMT via TGF-β signaling and may suggest novel radiation sensitise strategies for lung cancer.

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USP33 mediates Slit‐Robo signaling in inhibiting colorectal cancer cell migration

Cited by 54 publications

References 39 publications

USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma

USP33 is a Biomarker of Disease Recurrence in Papillary Thyroid Carcinoma

MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A

Radiation Enhances the Epithelial– Mesenchymal Transition of A549 Cells via miR3591-5p/USP33/PPM1A

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