Small interference RNA-mediated knockdown of sperm associated antigen 9 having structural homology with c-Jun N-terminal kinase-interacting protein

Rana, Ritu; Jagadish, Nirmala; Garg, Manoj; Mishra, Deepshikha; Dahiya, Neetu; Chaurasiya, Dipak; Suri, Anil

doi:10.1016/j.bbrc.2005.11.168

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…16 Others have demonstrated prognostic impact of MAGEC1, SSX2 and CT45. 13,16,34,[39][40] A recently published signature for highrisk disease contains the genes GAGE1 and GAGE12 which further confirms the relationship between CTA genes and prognosis. 41 Cancer testis antigen expression in MM haematologica | 2011; 96 (11)Cluster analysis further confirms the correlation between different CTAs and especially those located on chromosome X.…”

Section: Discussionmentioning

confidence: 52%

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Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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Section: Discussionmentioning

confidence: 52%

“…SPAG9 is present in all but one sample in this study, and has been described to mediate JNK signaling. [34][35] For immunotherapy, expression in normal tissues raises concerns of generating autoimmune responses following vaccination. Still, some TS antigens, like MAGEA3, are targeted in current immunotherapeutic protocols.…”

Section: Discussionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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“…Four RCC cell lines from American Type Culture Collection and three established RCC cell lines from patients with primary RCC of clear cell type were used and cultured following standard procedures. Transient transfections were performed using Lipofectamine reagent (Invitrogen Life Technologies) according to the manufacturer's instruction as described earlier (20). Established cell lines were obtained after tumor cell suspension preparation as described in Supplementary Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

“…The BS/U6 vector was used to construct two SPAG9-specific siRNA (SPAG9 siRNA and SPAG9 siRNA-I) and control siRNA (scrambled SPAG9) as described previously (20). The cloning strategy and protocol is described in Supplementary Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

et al. 2008

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Renal cell carcinoma (RCC) represents one of the most resistant tumors to radiation and chemotherapy. Current therapies for RCC patients are inefficient due to the lack of diagnostic and therapeutic markers. Our recent studies have suggested an association of sperm-associated antigen 9 (SPAG9) with ovarian carcinomas. In the present study, we investigated the clinical relevance of SPAG9 in RCC patients. RT-PCR analysis showed expression of SPAG9 transcript in RCC tissues and RCC cell lines. In situ RNA hybridization and immunohistochemistry analyses confirmed the expression of SPAG9 in 88% of cancer patients, suggesting that SPAG9 participates in renal cancer. In addition, immunoblotting and ELISA analyses revealed a humoral immune response against SPAG9 in the sera of RCC patients but not in healthy individuals. Consistent with the clinical findings, knockdown of SPAG9 expression in RCC cells with specific siRNA significantly reduced cell growth and colony formation. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also significantly inhibited. Furthermore, in vivo xenograft studies in nude mice revealed that administration of a SPAG9 siRNA plasmid significantly inhibited tumor growth. In conclusion, SPAG9 expression is associated with clinicopathologic features of tumors, suggesting that SPAG9 could contribute to the early spread of cancer. These results indicate that SPAG9 may have a role in tumor development and metastasis and thus could serve as a novel target for early detection and treatment of RCC. [Cancer Res 2008;68(20):8240-8]

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“…The BS/U6 vector was used to construct SPAG9 small interfering RNA ( SPAG9 small interfering RNA and SPAG9 small interfering RNA‐I) and control small interfering RNA (scrambled SPAG9 ), as described previously 16. SiHa cells, SCC‐derived cervical cancer cells, were used to determine small interfering RNA‐mediated knockdown of SPAG9 .…”

Section: Methodsmentioning

confidence: 99%

Small interfering RNA‐mediated down‐regulation of SPAG9 inhibits cervical tumor growth

Garg

Kanojia

Suri

et al. 2009

Cancer

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BACKGROUND: The expression of the SPAG9 is associated with various human malignancies. Earlier work revealed a significant association of SPAG9 expression with the early spread of cervical cancer, making it an attractive therapeutic target. Here, the authors investigated the role of SPAG9 in carcinogenesis of squamous cell carcinoma (SCC) of the cervix. Furthermore, they sought to determine whether ablation of SPAG9 expression reduces the tumor growth of cervical SCC in vivo. METHODS: A plasmid‐based small interfering RNA approach was used to specifically knock down the expression of SPAG9 in SiHa cells derived from SCC of the cervix in vitro and in vivo. Reverse transcriptase polymerase chain reaction, immunofluorescence staining, flow cytometry, cellular growth, colony formation, migration, invasion, and wound healing assays were studied to characterize SPAG9 in vitro. Furthermore, a cervical cancer xenograft model in nude mice was established to investigate whether knockdown of SPAG9 reduces the tumor growth of cervical SCC in vivo. RESULTS: The results demonstrated that silencing the SPAG9 by small interfering RNA resulted in inhibition of cell growth, colony formation, migration, and invasion. The authors showed for the first time that the knockdown of SPAG9 expression by small interfering RNA significantly suppressed the tumor growth of cervical SCC in vivo. CONCLUSIONS: These results suggest that SPAG9 expression may play a pivotal role in tumor growth and could contribute to the early spread of cervical cancer. Small interfering RNA‐mediated down‐regulation of SPAG9 represents a promising therapeutic approach for the treatment of cervical cancer. Cancer 2009. © 2009 American Cancer Society.

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Small interference RNA-mediated knockdown of sperm associated antigen 9 having structural homology with c-Jun N-terminal kinase-interacting protein

Cited by 11 publications

References 27 publications

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Sperm-Associated Antigen 9 Is Associated With Tumor Growth, Migration, and Invasion in Renal Cell Carcinoma

Small interfering RNA‐mediated down‐regulation of SPAG9 inhibits cervical tumor growth

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