Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer cells in vitro

Wang, Haibo; Ji, Xiaojun; Liu, Xiangping; Yao, Ruyong; Chi, Jen-Tsan; Liu, Shihai; Wang, Yu; Cao, Weihong; Zhou, Quan

doi:10.3892/or.2013.2798

Cited by 39 publications

(50 citation statements)

References 29 publications

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“…The present observations are consistent with the recent discovery that endogenous shRNA expression is enhanced by miRNAs (30,31). However, it is important to note that conventional stem-loop shRNAs, such as those used previously in lentiviruses (18), are not processed into functional siRNAs under certain conditions. The inducible expression of transgenes provides an improved level of safety since it avoids much of the unintended consequences of viral vector-mediated delivery and gene silencing.…”

Section: Discussionsupporting

confidence: 80%

“…We found that suppression of USP39 in TNBC cell lines was key to their capacity for growth. Transient shRNA silencing by the USP39 lentivirus in MCF-7 cells partially recapitulated the aggressive basal phenotype (18). These effects on migration were independent of cell replication.…”

Section: Discussionmentioning

confidence: 87%

“…Supernatants were collected 48 h after transfection, filtered through a 0.4-µm membrane and used to infect the cells. The cells were infected and the percentage of GFP/mCherry-positive cells was determined to ensure that the majority of cells contained the lentiviruses (18).…”

Section: Methodsmentioning

confidence: 99%

“…As the downregulation of USP39 was previously reported to suppress the growth of breast cancer cells in our laboratory (18), we first performed short-term assays in which our inducible-USP39 cell lines were stimulated with DOX prior to counting the total number of cells.…”

Section: Usp39 Overexpression Does Not Promote Cancer Cell Proliferatmentioning

confidence: 99%

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Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

Liu

Wang

et al. 2015

Oncology Reports

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Abstract. Triple-negative breast cancer (TNBC), characterized by distinct biological and clinicopathological features, has a poor prognosis due to lack of effective therapeutic targets. Our previous data revealed that high levels of USP39 were selectively present in TNBC samples compared with their normal breast tissue samples and USP39 was also expressed at different levels in cultured TNBC cells and normal breast cells. Yet, the underlying cellular and molecular mechanisms of USP39 remain unclear. In the present study, we describe a doxycycline (DOX)-regulated lentiviral vector system expressing shRNA or cDNA of the USP39 gene in the TNBC cell line MDA-MB-231. USP39 expression was knocked down by the miR-30-based inducible lentiviral short hairpin RNA (shRNA) delivery system or overexpressed by the inducible cDNA system. The inducible shRNA-mediated downregulation of USP39 expression markedly reduced the proliferation and colony-forming ability of MDA-MB-231 cells, while overexpression of USP39 by the inducible system did not promote cancer cell proliferation. The lentiviral vector-mediated Tet-on system demonstrated efficient and inducible knockdown of USP39 or overexpression of USP39 in TNBC cells, facilitating a wide variety of applications for gene knockdown and overexpression experiments in gene functional studies in vitro and in vivo.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Usp39 Overexpression Does Not Promote Cancer Cell Proliferatmentioning

confidence: 99%

See 2 more Smart Citations

Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

Liu

Wang

et al. 2015

Oncology Reports

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“…Some more recent studies have reported the involvement of USP39 in malignant cell growth. 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.…”

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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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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The SUMOylation and ubiquitination crosstalk in cancer

Li,

Xia,

et al. 2023

J Cancer Res Clin Oncol

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Lentivirus-mediated inhibition of USP39 suppresses the growth of breast cancer cells in vitro

Cited by 39 publications

References 29 publications

Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

Lentiviral vector-mediated doxycycline-inducible USP39 shRNA or cDNA expression in triple-negative breast cancer cells

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

The SUMOylation and ubiquitination crosstalk in cancer

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