American Association for Cancer Research
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Supplementary Methods, Figures 1 - 8, Table 1 from TNRC9 Downregulates BRCA1 Expression and Promotes Breast Cancer Aggressiveness

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journal contribution
posted on 2023-03-30, 22:09 authored by Jingxuan Shan, Shoba P. DSouza, Sasha Bakhru, Eman K. Al-Azwani, Maria L. Ascierto, Konduru S. Sastry, Shahinaz Bedri, Dhanya Kizhakayil, Idil I. Aigha, Joel Malek, Issam Al-Bozom, Salah Gehani, Stacia Furtado, Edith Mathiowitz, Ena Wang, Francesco M. Marincola, Lotfi Chouchane

PDF file - 655K, Supplementary Figure 1. TNRC9 promoted cell proliferation in MDA-MB-231 breast cancer cells. Supplementary Figure 2. shRNA-mediated knockdown of TNRC9. Supplementary Figure 3. H&E staining of tumors (10�Magnification) from xenograft nude mice subcutaneously injected with control ZR-75-1cells (upper row I � V) were compared with those injected with TNRC9-depeltion ZR-75-1 cells (lower row VI � VIII, no palpable tumor in two mice). �-� represents 400μm. Supplementary Figure 4. Knocking-down TNRC9 sensitizes cancer cells to apoptosis signal. Supplementary Figure 5. BRCA1 and TNRC9 expression in TNRC9 abrogated and control cells. Supplementary Figure 6. The expression profile of TNRC9 knockdown MCF-7 cells. Supplementary Figure 7. In silico analysis of TNRC9 and BRCA1 gene expression among ovarian cancer patients. Supplementary Figure 8. The effects of TNRC9 on luciferase activity driven by BRCA1 promoter. Supplementary Table 1 The list of transcripts significantly altered in TNRC9 knockdown MCF-7 cells comparing to control MCF-7 cells



Although the linkage between germline mutations of BRCA1 and hereditary breast/ovarian cancers is well established, recent evidence suggests that altered expression of wild-type BRCA1 might contribute to the sporadic forms of breast cancer. The breast cancer gene trinucleotide-repeat-containing 9 (TNRC9; TOX3) has been associated with disease susceptibility but its function is undetermined. Here, we report that TNRC9 is often amplified and overexpressed in breast cancer, particularly in advanced breast cancer. Gene amplification was associated with reduced disease-free and metastasis-free survival rates. Ectopic expression of TNRC9 increased breast cancer cell proliferation, migration, and survival after exposure to apoptotic stimuli. These phenotypes were associated with tumor progression in a mouse model of breast cancer. Gene expression profiling, protein analysis, and in silico assays of large datasets of breast and ovarian cancer samples suggested that TNRC9 and BRCA1 expression were inversely correlated. Notably, we found that TNRC9 bound to both the BRCA1 promoter and the cAMP-responsive element-binding protein (CREB) complex, a regulator of BRCA1 transcription. In support of this connection, expression of TNRC9 downregulated expression of BRCA1 by altering the methylation status of its promoter. Our studies unveil a function for TNRC9 in breast cancer that highlights a new paradigm in BRCA1 regulation. Cancer Res; 73(9); 2840–9. ©2013 AACR.

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