Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT

Yan, Congcong; Yuan, Jiahui; Xu, Jiajia; Zhang, Gongye; Li, Xiaomei; Zhang, Bing; Hu, Tianhui; Huang, Xiaohua; Mao, Yonghui; Song, Gang

doi:10.1007/s12032-019-1308-7

Cited by 21 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study has revealed that p53 induces p21 stable expression through promoter binding 37 . A recent report has discovered that knockdown of USP39 inhibits the proliferation process of human ovarian cancer via p53/p21 pathway 12 . However, our results indicated that USP39 depletion causes the upregulation of p53 and p21, and that the regulation of p21 expression is independent of p53.…”

Section: Discussioncontrasting

confidence: 73%

“…A 150‐spot, paraffin‐embedded, human colon cancer tissue microarray (COC1261) containing 75 paired colon cancer tumor and para‐tumor tissues was purchased from Fanpu Biotech, Inc. Immunohistochemistry (IHC) staining was performed as previously described 28 . The positive ration of USP39 protein in colon cancer tissues was determined as previously described 12 …”

Section: Methodsmentioning

confidence: 99%

“…Total RNA from HCT116 cells was extracted and the mRNA levels of USP39 and p21 were detected as previously described 12 . The gene‐specific primer sequences were shown as follows:…”

Section: Methodsmentioning

confidence: 99%

“…Belonging to the ubiquitin‐specific proteins family, USP39 contains an N‐terminal RS‐like ZNF domain and a C‐terminal ubiquitin hydrolase domain 8 . Studies have demonstrated that USP39 exhibits diverse biological functions in multiple malignancies, such as cell mitosis, 9 cell cycle progression, apoptosis, 10,11 cell invasion and metastasis, 12 DNA damage repair, 13 pre‐messenger RNA (mRNA) splicing, 14–16 and platinum resistance 13,17 . Previous studies have reported that USP39 knockdown inhibits colon cancer cell growth, induces cell apoptosis and suppresses metastasis via the regulation WNT/β‐catenin pathway 18 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

USP39 mediates p21‐dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis

Yuan

Zhang

et al. 2021

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

Ubiquitin‐specific protease 39 (USP39) is frequently overexpressed in a variety of cancers, and involved in the regulation of various biological processes, such as cell proliferation, cell cycle progression, apoptosis and pre‐messenger RNA splicing. Nevertheless, the biological roles and mechanisms of USP39 in colon cancer remain largely unknown. In this study, we analyzed whether USP39 can be a molecular target for the treatment of colon cancer. Whilst overexpression of USP39 was detected in human colon cancer tissues and cell lines, USP39 knockdown was observed to inhibit the growth and subcutaneous tumor formation of colon cancer cells. Further analysis showed that USP39 knockdown can stabilize p21 by prolonging the half‐life of p21 and by upregulating the promoter activity of p21. The RS domain and USP domain of USP39 were found to play an essential role. Additionally, our findings revealed that USP39 plays a regulatory role in the proliferation of colon cancer cells by the p53/p21/CDC2/cyclin B1 axis in a p21‐dependent manner. Taken together, this study provided the theoretical basis that may facilitate the development of USP39 as a novel potential target of colon cancer therapy.

show abstract

Section: Discussioncontrasting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

“…Total RNA from HCT116 cells was extracted and the mRNA levels of USP39 and p21 were detected as previously described 12 . The gene‐specific primer sequences were shown as follows:…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

USP39 mediates p21‐dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis

Yuan

Zhang

et al. 2021

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Splicing factors can act as both oncoproteins and tumor suppressors 24 . Previous studies have shown that USP39 is commonly upregulated in various human cancers including ovarian cancer 25,26 . High USP39 expression is correlated with poor prognosis in patients with prostate and gastric cancers 27,28 .…”

Section: Discussionmentioning

confidence: 99%

Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

Wang

et al. 2021

Cell Death Dis

View full text Add to dashboard Cite

Aberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

show abstract

Long noncoding RNA ST8SIA6‐AS1 promotes cell proliferation and metastasis in triple‐negative breast cancer by targeting miR‐145‐5p/CDCA3 to inactivate the p53/p21 signaling pathway

Qiao

Wang

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Background: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, always exhibits a poor prognosis due to high risk of early recurrence and distant metastasis. Long noncoding RNAs (lncRNAs) have been reported as crucial regulators in breast cancer. However, the functions and action mechanisms of lncRNA ST8SIA6-AS1 in TNBC are largely unknown. Methods: Quantitative real-time PCR and western blot assays were used to measure the expression levels of different genes and proteins. Cell proliferation ability was monitored by CCK-8, colony forming and flow cytometry assays. Wound healing and transwell assays were performed to evaluate cell migration and invasion. The regulatory mechanisms of ST8SIA6-AS1 in TNBC were confirmed by dual luciferase reporter and RIP assays. A mouse xenograft model was established to investigate the role of ST8SIA6-AS1 in TNBC tumor growth. Results: ST8SIA6-AS1 displayed a higher expression in TNBC cells. Silencing ST8SIA6-AS1 impaired cell proliferation, cell cycle progression, migration, and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, ST8SIA6-AS1 could facilitate the expression of its target CDCA3 (cell division cycle associated protein 3) and inactivate the p53/p21 signaling by inhibiting miR-145-5p. Moreover, miR-145-5p exerted a tumor-suppressive activity by targeting CDCA3. The tumorsuppressive effects induced by ST8SIA6-AS1 knockdown were abated by the downregulation of miR-145-5p or the up-regulation of CDCA3. Conclusion: ST8SIA6-AS1 exerts an oncogenic role in TNBC by interacting with miR-145-5p to up-regulate CDCA3 expression and inactivate the p53/p21 signaling, highlighting ST8SIA6-AS1 as a promising molecular target to combat TNBC.

show abstract

Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT

Cited by 21 publications

References 35 publications

USP39 mediates p21‐dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis

USP39 mediates p21‐dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis

Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

Long noncoding RNA ST8SIA6‐AS1 promotes cell proliferation and metastasis in triple‐negative breast cancer by targeting miR‐145‐5p/CDCA3 to inactivate the p53/p21 signaling pathway

Contact Info

Product

Resources

About