Comprehensive Analysis of Mouse Cancer/Testis Antigen Functions in Cancer Cells and Roles of TEKT5 in Cancer Cells and Testicular Germ Cells

ABSTRACT The cancer/testis antigen (CTA) genes were identified as human genes preferentially expressed in cancer cells and testis, but the contribution of CTAs to cancer and male germ cell development is unclear. In this study, we comprehensively examined mouse CTA functions and found that the majority of CTAs are involved in growth and/or survival of cancer cells. We focused on one mouse CTA gene, Tekt5, for its detailed functional analysis. Tekt5 knockdown (KD) in ovarian cancer cells caused G1 arrest and apoptosis, and p27kip1 was concomitantly upregulated. Tekt5 KD also resulted in decreased levels of acetylated α-tubulin and subsequent fragmentation of β-III-tubulin, upregulation of HDAC6 that deacetylates α-tubulin, and nuclear accumulation of SMAD3 that induces p27kip1 expression. Because depolymerization of tubulin is known to cause translocation of SMAD3 to the nucleus, these results together suggested that TEKT5 negatively regulates Hdac6 expression and consequently maintains cell cycle via stabilization of tubulin. We also found that the number of spermatids was significantly decreased and acetylated α-tubulin levels were decreased in vivo by KD of Tekt5 in testis. Because acetylated α-tubulin is required for sperm morphogenesis, these results suggest that TEKT5 is necessary for spermiogenesis via maintenance of acetylated α-tubulin levels.

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Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1

Journal of International Medical Research ◽

10.1177/03000605211040762 ◽

2021 ◽

Vol 49 (9) ◽

pp. 030006052110407

Author(s):

Jianxiu Duan ◽

Mingyuan Yin ◽

Yaqin Shao ◽

Jiao Zheng ◽

Shengdan Nie

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Sirtuin 1 ◽

Nuclear Accumulation ◽

Ovarian Cancer Cells ◽

Platinum Resistant

Objective Previous investigations indicated the anticancer activity of puerarin. The current study aimed to evaluate the effect and molecular mechanisms of puerarin in chemotherapy-resistant ovarian cancer cells. Methods We examined the effects of puerarin in platinum-resistant epithelial ovarian cancer cells in vitro and in vivo. We also analyzed the molecular mechanism underlying Wnt/β-catenin inhibition and sirtuin 1 (SIRT1) regulation following puerarin treatment. Results Our study demonstrated that puerarin effectively inhibited cell growth in vitro and in vivo by increasing apoptosis in ovarian cancer cells. More importantly, puerarin sensitized cisplatin-resistant ovarian cancer cells to chemotherapy. Puerarin treatment decreased SIRT1 expression, which attenuated the nuclear accumulation of β-catenin to inhibit Wnt/β-catenin signaling. In addition, SIRT1 overexpression diminished the effects of puerarin treatment on cisplatin-resistant ovarian cancer cells. Further analysis supported SIRT1/β-catenin expression as a candidate biomarker for the disease progression of epithelial ovarian cancer. Conclusions Puerarin increased the apoptosis of platinum-resistant ovarian cancer cells. The mechanism is partly related to the downregulation of SIRT1 and subsequent inhibition of Wnt/β-catenin signaling.

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Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

Science Advances ◽

10.1126/sciadv.abb0737 ◽

2021 ◽

Vol 7 (9) ◽

pp. eabb0737

Author(s):

Zhengnan Yang ◽

Wei Wang ◽

Linjie Zhao ◽

Xin Wang ◽

Ryan C. Gimple ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Plasma Cell ◽

Plasma Cells ◽

Ovarian Cancer Cells ◽

Mesenchymal Phenotype ◽

Ovarian Cancers ◽

Novel Approach

Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.

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

Cell Death and Disease ◽

10.1038/s41419-021-03581-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Shourong Wang ◽

Zixiang Wang ◽

Jieyin Li ◽

Junchao Qin ◽

Jianping Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Malignant Tumors ◽

Splicing Factor ◽

Ovarian Cancer Cells ◽

Nuclear Speckles ◽

Aberrant Expression ◽

Intergenic Regions

AbstractAberrant 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.

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Combined chemotherapy and allogeneic human Vγ9Vδ2 T lymphocyte-immunotherapies efficiently control the development of human epithelial ovarian cancer cells in vivo

OncoImmunology ◽

10.1080/2162402x.2019.1649971 ◽

2019 ◽

Vol 8 (11) ◽

pp. e1649971 ◽

Cited By ~ 2

Author(s):

Noémie Joalland ◽

Laura Lafrance ◽

Thibauld Oullier ◽

Séverine Marionneau-Lambot ◽

Delphine Loussouarn ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

T Lymphocyte ◽

Ovarian Cancer Cells ◽

Combined Chemotherapy

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Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo

Laboratory Investigation ◽

10.1038/labinvest.2015.132 ◽

2015 ◽

Vol 96 (1) ◽

pp. 37-48 ◽

Cited By ~ 18

Author(s):

Yanyan Ma ◽

Zengtao Wei ◽

Robert C Bast ◽

Zhanying Wang ◽

Yan Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells

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BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and β1 integrin expression in ovarian cancer cells

British Journal of Cancer ◽

10.1038/sj.bjc.6690448 ◽

1999 ◽

Vol 80 (7) ◽

pp. 946-953 ◽

Cited By ~ 64

Author(s):

J M Runnels ◽

N Chen ◽

B Ortel ◽

D Kato ◽

T Hasan

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cellular Adhesion ◽

Ovarian Cancer Cells ◽

Β1 Integrin ◽

Integrin Expression

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The role of Sox6 and Netrin-1 in ovarian cancer cell growth, invasiveness, and angiogenesis

Tumor Biology ◽

10.1177/1010428317705508 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770550 ◽

Cited By ~ 4

Author(s):

Yi Li ◽

Ming Xiao ◽

Fangchun Guo

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Conditioned Medium ◽

Umbilical Vein ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Human Umbilical Vein ◽

Tumor Tissues

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.

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