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8. Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction.

Author

Mir, Shakeel, Ormsbee Golden, Briana D., Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Subjects
METASTATIC breast cancer, FIBROBLASTS, NUCLEIC acid hybridization, NUCLEAR factor E2 related factor, NADPH oxidase, ORTHOKERATOLOGY
Abstract

Background: A pro-oxidant enzyme, NADPH oxidase 4 (Nox4) has been reported to be a critical downstream effector of TGFβ-induced myofibroblast transformation during fibrosis. While there are a small number of studies suggesting an oncogenic role of Nox4 derived from activated fibroblasts, direct evidence linking this pro-oxidant to the tumor-supporting CAF phenotype and the mechanisms involved are lacking, particularly in breast cancer. Methods: We targeted Nox4 in breast patient-derived CAFs via siRNA-mediated knockdown or administration of a pharmaceutical inhibitor (GKT137831). We also determine primary tumor growth and metastasis of implanted tumor cells using a stable Nox4-/- syngeneic mouse model. Autophagic flux of CAFs was assessed using a tandem fluorescent-tagged ptfl-LC3 plasmid via confocal microscopy analysis and determination of the expression level of autophagy markers (beclin-1 and LC3B). Nox4 overexpressing CAFs depend on the Nrf2 (nuclear factor-erythroid factor 2-related factor 2) pathway for survival. We then determined the dependency of Nox4-overexpressing CAFs on the Nrf2-mediated adaptive stress response pathway for survival. Furthermore, we investigated the involvement of Birc5 on CAF phenotype (viability and collagen contraction activity) as well as the expression level of CAF markers, FAP and αSMA. Conclusions: We found that deletion of stroma Nox4 and pharmaceutically targeting its activity with GKT137831 significantly inhibited orthotopic tumor growth and metastasis of implanted E0771 and 4T1 murine mammary carcinoma cell lines in mice. More importantly, we found a significant upregulation of Nox4 expression in CAFs isolated from human breast tumors versus normal mammary fibroblasts (RMFs). Our in situ RNA hybridization analysis for Nox4 transcription on a human breast tumor microarray further support a role of this pro-oxidant in the stroma of breast carcinomas. In addition, we found that Nox4 promotes autophagy in CAFs. Moreover, we found that Nox4 promoted survival of CAFs via activation of Nrf2, a master regulator of oxidative stress response. We have further shown Birc5 is involved as a downstream modulator of Nrf2-mediated pro-survival phenotype. Together these studies indicate a role of redox signaling via the Nox4-Nrf2 pathway in tumorigenesis and metastasis of breast cancer cells by promoting autophagy and survival of CAFs. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis

Author

Kaushik, Garima, Seshacharyulu, Parthasarathy, Rauth, Sanchita, Nallasamy, Palanisamy, Rachagani, Satyanarayana, Nimmakayala, Rama Krishna, Vengoji, Raghupathy, Mallya, Kavita, Chirravuri-Venkata, Ramakanth, Singh, Amar B., Foster, Jason M., Ly, Quan P., Smith, Lynette M., Lele, Subodh M., Malafa, Mokenge P., Jain, Maneesh, Ponnusamy, Moorthy P., and Batra, Surinder K.

Published
2021
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11. Cancer-associated Fibroblast Induces Acinar-to-ductal Cell Transdifferentiation and Pancreatic Cancer Initiation via LAMA5/ITGA4 axis

Author

Parte, Seema, primary, Kaur, Annant B., additional, Nimmakayala, Rama Krishna, additional, Ogunleye, Ayoola O., additional, Chirravuri, Ramakanth, additional, Vengoji, Raghupathy, additional, Leon, Frank, additional, Nallasamy, Palanisamy, additional, Rauth, Sanchita, additional, Alsafwani, Zahraa Wajih, additional, Lele, Subodh, additional, Cox, Jesse L., additional, Bhat, Ishfaq, additional, Singh, Shailender, additional, Batra, Surinder K., additional, and Ponnusamy, Moorthy P., additional

Published
2023
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14. Cigarette Smoke Induces Stem Cell Features of Pancreatic Cancer Cells via PAF1

Author

Nimmakayala, Rama Krishna, Seshacharyulu, Parthasarathy, Lakshmanan, Imayavaramban, Rachagani, Satyanarayana, Chugh, Seema, Karmakar, Saswati, Rauth, Sanchita, Vengoji, Raghupathy, Atri, Pranita, Talmon, Geoffrey A., Lele, Subodh M., Smith, Lynette M., Thapa, Ishwor, Bastola, Dhundy, Ouellette, Michel M., Batra, Surinder K., and Ponnusamy, Moorthy P.

Published
2018
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15. Supplementary Figure 11 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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16. Supplementary Revised Figure S3 from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53

Author

Lakshmanan, Imayavaramban, primary, Salfity, Shereen, primary, Seshacharyulu, Parthasarathy, primary, Rachagani, Satyanarayana, primary, Thomas, Abigail, primary, Das, Srustidhar, primary, Majhi, Prabin D., primary, Nimmakayala, Rama Krishna, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Ponnusamy, Moorthy P., primary, Batra, Surinder K., primary, and Ganti, Apar Kishor, primary

Published
2023
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17. Supplementary Figure 4 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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18. Data from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53

Author

Lakshmanan, Imayavaramban, primary, Salfity, Shereen, primary, Seshacharyulu, Parthasarathy, primary, Rachagani, Satyanarayana, primary, Thomas, Abigail, primary, Das, Srustidhar, primary, Majhi, Prabin D., primary, Nimmakayala, Rama Krishna, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Ponnusamy, Moorthy P., primary, Batra, Surinder K., primary, and Ganti, Apar Kishor, primary

Published
2023
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19. Supplementary Figure 5 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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20. Supplementary Figure 8 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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21. Supplementary Figure 2 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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22. Supplementary Figure 9 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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23. Supplementary Figure legends from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53

Author

Lakshmanan, Imayavaramban, primary, Salfity, Shereen, primary, Seshacharyulu, Parthasarathy, primary, Rachagani, Satyanarayana, primary, Thomas, Abigail, primary, Das, Srustidhar, primary, Majhi, Prabin D., primary, Nimmakayala, Rama Krishna, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Ponnusamy, Moorthy P., primary, Batra, Surinder K., primary, and Ganti, Apar Kishor, primary

Published
2023
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24. Supplementary Figure 7 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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25. Supplementary Table 1 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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26. Supplementary Figure 3 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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27. Supplementary Figure 6 from PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, primary, Chirravuri Venkata, Ramakanth, primary, Marimuthu, Saravanakumar, primary, Nallasamy, Palanisamy, primary, Vengoji, Raghupathy, primary, Lele, Subodh M., primary, Rachagani, Satyanarayana, primary, Mallya, Kavita, primary, Malafa, Mokenge P., primary, Ponnusamy, Moorthy P., primary, and Batra, Surinder K., primary

Published
2023
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29. Elevated PAF1-RAD52 axis confers chemoresistance to human cancers

Author

Rauth, Sanchita, primary, Ganguly, Koelina, additional, Atri, Pranita, additional, Parte, Seema, additional, Nimmakayala, Rama Krishna, additional, Varadharaj, Venkatesh, additional, Nallasamy, Palanisamy, additional, Vengoji, Raghupathy, additional, Ogunleye, Ayoola O., additional, Lakshmanan, Imayavaramban, additional, Chirravuri, Ramakanth, additional, Bessho, Mika, additional, Cox, Jesse L., additional, Foster, Jason M., additional, Talmon, Geoffrey A., additional, Bessho, Tadayoshi, additional, Ganti, Apar Kishor, additional, Batra, Surinder K., additional, and Ponnusamy, Moorthy P., additional

Published
2023
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30. MEDB-90. Iron Imbalance Can Potentiate Cisplatin Response in Pediatric Medulloblastoma by Regulating Ferroptosis

Author

Kanchan, Ranjana, primary, Perumal, Naveenkumar, additional, Khan, Parvez, additional, Doss, David, additional, Venkata, Ramakanth Chirravuri, additional, Thapa, Ishwor, additional, Vengoji, Raghupathy, additional, Kaushal, Jyoti, additional, Siddiqui, Jawed, additional, Nasser, Mohd Wasim, additional, Batra, Surinder, additional, and Mahapatra, Sidhartha, additional

Published
2022
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31. Additional file 4 of Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction

Author

Mir, Shakeel, Golden, Briana D. Ormsbee, Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Abstract

Additional file4: Fig S4. Extracellular H2O2 levels in Nox4 overexpressing RMF. Nox4 expression (both wild type and the inactive mutant form) was induced with 100 ng/mL of doxycycline for 24 h and 48 h prior to AmplexRed assay. Extracellular H2O2 was measured after 30 min of reagent incubation. Error bars are standard deviations of mean from 3 separate samples. * p < 0.01 versus RMF at 48h.

Published
2022
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32. Additional file 3 of Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction

Author

Mir, Shakeel, Golden, Briana D. Ormsbee, Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Abstract

Additional file3: Fig S3. Activated phenotype of CAF5. (A and B) Fibroblasts were embedded in collagen matrix. Surface areas of the contracted collagen disc after 8 h were analyzed with ImageJ and presented in the bar graph. Pictures show representative triplicate of contracted collagen discs from N = 3 independent experiments. Data are mean ± SD of N = 3. * p < 0.05 in GKT treated samples versus DMSO. # p < 0.05 vs untreated CAF5. (C) Migration of breast cancer cells when co-cultured with CAF5. The two cell types were seeded separately in ibidi culture inserts. When cells reached confluence, the inserts were removed to allow cells to migrate w/wo GKT137831 (20 μM). After 16 h of migration, stained of migration, cells were imaged for quantification by ImageJ, as shown in (D). Data are mean ± SD of N = 3 independent experiments. * p < 0.05 in CAF5 versus RMF. # p < 0.05 in GKT treated CAF5 vs untreated CAF5. (E) GKT137831 effectively reduced cellular ROS levels in CAF5, as demonstrated by the levels of H2O2 released into the cell culture media via AmplexRed assay. * p < 0.05 vs untreated RMF. # p < 0.05 in GKT treated CAF5 vs untreated CAF5. Data are mean ± SD of N = 3 independent experiments.

Published
2022
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33. Additional file 2 of Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction

Author

Mir, Shakeel, Golden, Briana D. Ormsbee, Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Abstract

Additional file2: Fig S2. Real time PCR analysis showing relative mRNA expression of (A) p22phox in CAFs vs RMF. * represent P < 0.05 vs RMF, N = 3. Error bars are standard deviation of N =3.

Published
2022
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34. Additional file 1 of Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction

Author

Mir, Shakeel, Golden, Briana D. Ormsbee, Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Abstract

Additional file1: Fig. S1. Nox4-derived ROS does not contribute to macrophage phenotype. (A) Primary human monocytes were treated with an antioxidant, MnTE or GKT137831 during differentiation and polarization to M1 or M2 macrophages and analyzed for the mRNA expression of M2 markers, IL-10. (B) GKT137831-treated macrophages were also analyzed for extracellular release of ROS by AmplexRed assay. * represent P < 0.05 vs untreated control. Error bars are standard deviation of N =3.

Published
2022
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35. Additional file 5 of Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction

Author

Mir, Shakeel, Golden, Briana D. Ormsbee, Griess, Brandon J., Vengoji, Raghupathy, Tom, Eric, Kosmacek, Elizabeth A., Oberley-Deegan, Rebecca E., Talmon, Geoffrey A., Band, Vimla, and Teoh-Fitzgerald, Melissa LT.

Abstract

Additional file5: Fig. S5. CAFs are more tolerant to exogenous ROS insults compared to RMF. Confluent fibroblasts were treated with H2O2 at the indicated concentrations and viability was assessed by PrestoBlue reagent after 4, 8, and 16 hours of treatment. * represents P < 0.05 vs RMF and # represents p < 0.005 versus RMF, treated at the same dose of H2O2.

Published
2022
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36. MiR-1253 Potentiates Cisplatin Response in Pediatric Group 3 Medulloblastoma by Regulating Ferroptosis

Author

Kanchan, Ranjana K., primary, Perumal, Naveenkumar, additional, Khan, Parvez, additional, Doss, David, additional, Chirravuri Venkata, Ramakanth, additional, Thapa, Ishwor, additional, Vengoji, Raghupathy, additional, Kaushal, Jyoti, additional, Siddiqui, Jawed A., additional, Nasser, Mohd Wasim, additional, Batra, Surinder K., additional, and Mahapatra, Sidharth, additional

Published
2022
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37. Mucin 5AC Serves as the Nexus for β-Catenin/c-Myc Interplay to Promote Glutamine Dependency During Pancreatic Cancer Chemoresistance

Author

Ganguly, Koelina, primary, Bhatia, Rakesh, additional, Rauth, Sanchita, additional, Kisling, Andrew, additional, Atri, Pranita, additional, Thompson, Christopher, additional, Vengoji, Raghupathy, additional, Ram Krishn, Shiv, additional, Shinde, Dhananjay, additional, Thomas, Vinai, additional, Kaur, Sukhwinder, additional, Mallya, Kavita, additional, Cox, Jesse L., additional, Kumar, Sushil, additional, and Batra, Surinder K., additional

Published
2022
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38. Disruption of FDPS/Rac1 axis radiosensitizes pancreatic ductal adenocarcinoma by attenuating DNA damage response and immunosuppressive signalling

Author

Seshacharyulu, Parthasarathy, primary, Halder, Sushanta, additional, Nimmakayala, Ramakrishna, additional, Rachagani, Satyanarayana, additional, Chaudhary, Sanjib, additional, Atri, Pranita, additional, Chirravuri-Venkata, Ramakanth, additional, Ouellette, Michel M., additional, Carmicheal, Joseph, additional, Gautam, Shailendra K., additional, Vengoji, Raghupathy, additional, Wang, Shuo, additional, Li, Sicong, additional, Smith, Lynette, additional, Talmon, Geoffrey A., additional, Klute, Kelsey, additional, Ly, Quan, additional, Reames, Bradley N, additional, Grem, Jean L, additional, Berim, Lyudmyla, additional, Padussis, James C, additional, Kaur, Sukhwinder, additional, Kumar, Sushil, additional, Ponnusamy, Moorthy P., additional, Jain, Maneesh, additional, Lin, Chi, additional, and Batra, Surinder K, additional

Published
2022
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39. Reduction in O-glycome induces differentially glycosylated CD44 to promote stemness and metastasis in pancreatic cancer

Author

Leon, Frank, primary, Seshacharyulu, Parthasarathy, additional, Nimmakayala, Rama K., additional, Chugh, Seema, additional, Karmakar, Saswati, additional, Nallasamy, Palanisamy, additional, Vengoji, Raghupathy, additional, Rachagani, Satyanarayana, additional, Cox, Jesse L., additional, Mallya, Kavita, additional, Batra, Surinder K., additional, and Ponnusamy, Moorthy P., additional

Published
2021
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40. PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions

Author

Nimmakayala, Rama Krishna, primary, Rauth, Sanchita, additional, Chirravuri Venkata, Ramakanth, additional, Marimuthu, Saravanakumar, additional, Nallasamy, Palanisamy, additional, Vengoji, Raghupathy, additional, Lele, Subodh M., additional, Rachagani, Satyanarayana, additional, Mallya, Kavita, additional, Malafa, Mokenge P., additional, Ponnusamy, Moorthy P., additional, and Batra, Surinder K., additional

Published
2021
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41. Additional file 4 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 4: Fig. S3. Deregulated pathways associated with miR-212-3p silencing in group 3 MB. (A) Bubble plot (FunSet plot) representing 12 clusters of significantly enriched GO biological processes. FunSet employs hypergeometric test to perform the enrichments and additionally uses semantic similarity measure with Aggregate Information Content (AIC) index to cluster highly similar GO terms [17]. (B) Enriched biological pathways associated with miR-212-3p silencing identified using Enrichr ( https://maayanlab.cloud/Enrichr/ ) [4] highlighting regulation of cell cycle phase transition as the most enriched pathway in miR-212-3p overexpressed HDMB03 cells

Published
2021
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42. Additional file 3 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 3: Fig. S2. Effect of miR-212-3p expression on SHH MB cancer cells. (A) RT-PCR analysis showing increased miR-212-3p expression via transient transfection in Daoy cells. Growth restrictive properties demonstrable by (B) cell proliferation (MTT) and (C) colony formation assays in miR-212-3p transfected Daoy cells. Data presented as mean �� SD from experiments done in triplicate and analyzed using Student���s t-test; *p

Published
2021
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43. Additional file 1 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 1: Supplemental Methods

Published
2021
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44. Additional file 6 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 6: Fig. S4. Putative oncogenic targets of miR-212-3p and their associated pathways in group 3 MB tumors. (A) Expression analysis by RNA Sequencing of isolated miR-212-3p targets (37 genes) in local cohort of group 3 MB tumors (pediatric CB n=10; group 3 MB n=7; Kanchan et al., GSE148390). Those observed to be significantly elevated in group 3 tumors were the following 14 genes: CCDC71L, CTDSPL2, EDIL3, GIGYF1, HSBP1, KDM5A, NFIB, NRCAM, PSMA2, SDC2, SEPHS1, TAF4, TMEM43, and USP9X. (B) Enriched cellular/biological pathways associated with these targets identified using FunSet tool [17]. (C) Expression of NFIB across MB subgroups in a large MB meta-dataset (NC n=291; WNT n=118; SHH MB n=405; group 3 MB n=233; group 4 MB, n=530; Weishaupt et al., GSE124814). Box plots (A) represent gene expression (Log2 Transcripts Per Million) and were analyzed using Mann-Whiteny U test; *p

Published
2021
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45. Additional file 5 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 5: Table S1. Genes (and associated pathways) enriched by miR-212-3p expression restoration in HDMB03 cells. Detailed gene list for selected clusters of significantly enriched GO biological processes represented in Additional file 4: Fig. S3A. Presented clusters were selected based on -log10 FDR values with threshold p

Published
2021
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46. Additional file 7 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 7: Table S2. Isolating a strong oncogenic target of miR-212-3p. Further analysis of putative miR-212-3p targets by examining conserved binding sites, confirming elevated expression in 2 independent MB cohorts, and examining effect of high expression on survival. In the table, ���x��� denotes inclusion criteria, and ���-��� denotes no expression data found in dataset.

Published
2021
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47. Additional file 2 of MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB)

Author

Perumal, Naveenkumar, Kanchan, Ranjana K., Doss, David, Bastola, Noah, Atri, Pranita, Chirravuri-Venkata, Ramakanth, Thapa, Ishwor, Vengoji, Raghupathy, Maurya, Shailendra K., Klinkebiel, David, Talmon, Geoffrey A., Nasser, Mohd W., Batra, Surinder K., and Mahapatra, Sidharth

Abstract

Additional file 2: Fig. S1. Exploring epigenetic silencing of miR-212-3p in group 3 MB tumors. (A) Frequency distribution of cytogenetic aberrations (haploinsufficiency of 17p, i17q, c-Myc amplification) in (i) our local cohort of MB tumors (SHH n=9; group 3 MB n=10; group 4 MB n=16; Kanchan et al., GSE148390). (ii) Distinguishing features of high-risk tumors compared between our local cohort (Kanchan et al., GSE148390) and a larger dataset (Cavalli et al., GSE85217). (B) DNA methylation profile of local cohort of group 3 (n=6) and group 4 (n=11) MB tumors showing lack of perturbations to methylation in the promoter region of miR-212-3p compared to normal pediatric cerebellum (n=4); further demonstrable in vitro by a lack of expression restoration with de-methylation by 5-AzaC (5 ��M) in HDMB03 cells. (C) Recapitulation of elevated HDAC and EZH2 expression complementing prior in silico data in a large MB meta-dataset (NC n=291, group 3 MB n=233; Weishaupt et al., GSE124814). (D) RT-PCR analysis in pan-HDAC-treated D425 cells (TSA, 100 nM; Belinostat, 1 ��M; and Vorinostat, 1 ��M) showing elevated expression of miR-212-3p. RNU6B set as an endogenous control. Western blotting analysis showed increased acetylated ��-tubulin in pan-HDAC inhibitors treated D425 cells. ��-actin served as an internal control. Results presented as mean �� SD from experiments done in triplicate and analyzed using Student���s t-test (B and D) or Mann-Whiteny U test (C); *p

Published
2021
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48. ST6GalNAc‐I promotes lung cancer metastasis by altering MUC5AC sialylation

Author

Lakshmanan, Imayavaramban, primary, Chaudhary, Sanjib, additional, Vengoji, Raghupathy, additional, Seshacharyulu, Parthasarathy, additional, Rachagani, Satyanarayana, additional, Carmicheal, Joseph, additional, Jahan, Rahat, additional, Atri, Pranita, additional, Chirravuri‐Venkata, Ramakanth, additional, Gupta, Rohitesh, additional, Marimuthu, Saravanakumar, additional, Perumal, Naveenkumar, additional, Rauth, Sanchita, additional, Kaur, Sukhwinder, additional, Mallya, Kavita, additional, Smith, Lynette M., additional, Lele, Subodh M., additional, Ponnusamy, Moorthy P., additional, Nasser, Mohd W., additional, Salgia, Ravi, additional, Batra, Surinder K., additional, and Ganti, Apar Kishor, additional

Published
2021
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49. MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB)

Author

Perumal, Naveenkumar, primary, Kanchan, Ranjana K., additional, Doss, David, additional, Bastola, Noah, additional, Atri, Pranita, additional, Venkata, Ramakanth C., additional, Thapa, Ishwor, additional, Vengoji, Raghupathy, additional, Maurya, Shailendra K., additional, Klinkebiel, David, additional, Talmon, Geoffrey A., additional, Nasser, Mohd W., additional, Batra, Surinder K., additional, and Mahapatra, Sidharth, additional

Published
2021
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50. Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis

Author

Kaushik, Garima, primary, Seshacharyulu, Parthasarathy, additional, Rauth, Sanchita, additional, Nallasamy, Palanisamy, additional, Rachagani, Satyanarayana, additional, Nimmakayala, Rama Krishna, additional, Vengoji, Raghupathy, additional, Mallya, Kavita, additional, Chirravuri-Venkata, Ramakanth, additional, Singh, Amar B., additional, Foster, Jason M., additional, Ly, Quan P., additional, Smith, Lynette M., additional, Lele, Subodh M., additional, Malafa, Mokenge P., additional, Jain, Maneesh, additional, Ponnusamy, Moorthy P., additional, and Batra, Surinder K., additional

Published
2020
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