Basudeb Das

@nitrkl.ac.in

PhD Scholar in the Department of Life Science
National Institute of Technology Rourkela

Development of PIWI-interacting RNA (piRNA) - based diagnostic markers and therapies to treat cancer:
Deciphering mechanisms of dysregulation of piRNAs and their interplay with epigenetic regulators. Use piRNAs to restrict malignancy, increase chemotherapeutic sensitivity and targeted killing of malignant cancers.

EDUCATION

Master of Science (M. Sc.) in Human Physiology

RESEARCH INTERESTS

NcRNAs, Cancer, Molecular Physiology
12

Scopus Publications

344

Scholar Citations

11

Scholar h-index

12

Scholar i10-index

Scopus Publications

  • Corrigendum to “Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumor explants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways” Pathol. - Res. Pract. 237 (2022) 154029 (Pathology - Research and Practice (2022) 237, (S0344033822002734), (10.1016/j.prp.2022.154029))
    Sourav Kumar Nandi, Ayan Pradhan, Basudeb Das, Biswajit Das, Sudarshana Basu, et al.
    Pathology Research and Practice, 2024
  • Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumor explants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways
    Sourav Kumar Nandi, Ayan Pradhan, Basudeb Das, Biswajit Das, Sudarshana Basu, et al.
    Pathology Research and Practice, 2022
  • HIWI2 induces G2/M cell cycle arrest and apoptosis in human fibrosarcoma via the ROS/DNA damage/p53 axis
    Basudeb Das, Swapnil Sahoo, Bibekanand Mallick
    Life Sciences, 2022
  • Ribonucleotide reductase subunit M2 is a potential prognostic marker and therapeutic target for soft tissue sarcoma
    Basudeb Das, Neha Jain, Bibekanand Mallick
    Gene, 2022
    Soft tissue sarcomas (STS) are highly aggressive malignant tumors that exhibit poor therapeutic outcomes. Hence, we aimed to track down a potential gene that can be used as a prognostic marker and therapeutic target for this malignancy. We integrated omics analysis of clinical data and in vitro studies and identified Ribonucleotide reductase subunit M2 (RRM2) as a potential oncogene associated with STS prognosis. We found RRM2 is highly expressed in STS cell lines and tissues. STS patients with increased RRM2 levels showed worse overall survival, disease-free survival, progression-free survival, and disease-specific survival. Further, overexpression of RRM2 in HT1080 cells induces proliferation, migration, invasion, and colony formation, whereas its silencing arrest the cell cycle at G0/G1 phase and induces apoptosis. Taken together, we established RRM2 to be positively associated with oncogenesis and prognosis of STS and therefore could be a promising prognostic marker and therapeutic target.
  • miR-197-5p increases Doxorubicin-mediated anticancer cytotoxicity of HT1080 fibrosarcoma cells by decreasing drug efflux
    Neha Jain, Basudeb Das, Bibekanand Mallick
    DNA Repair, 2022
  • piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair
    Basudeb Das, Neha Jain, Bibekanand Mallick
    Communications Biology, 2021
    Resistance to doxorubicin (DOX) is an obstacle to successful sarcoma treatment and a cause of tumor relapse, with the underlying molecular mechanism still unknown. PIWI-interacting RNAs (piRNAs) have been shown to enhance patient outcomes in cancers. However, there are few or no reports on piRNAs affecting chemotherapy in cancers, including fibrosarcoma. The current study aims to investigate the relationship between piR-39980 and DOX resistance and the underlying mechanisms. We reveal that piR-39980 is less expressed in DOX-resistant HT1080 (HT1080/DOX) fibrosarcoma cells. Our results show that inhibition of piR-39980 in parental HT1080 cells induces DOX resistance by attenuating intracellular DOX accumulation, DOX-induced apoptosis, and anti-proliferative effects. Its overexpression in HT1080/DOX cells, on the other hand, increases DOX sensitivity by promoting intracellular DOX accumulation, DNA damage, and apoptosis. The dual-luciferase reporter assay indicates that piR-39980 negatively regulates RRM2 and CYP1A2 via direct binding to their 3′UTRs. Furthermore, overexpressing RRM2 induces DOX resistance of HT1080 cells by rescuing DOX-induced DNA damage by promoting DNA repair, whereas CYP1A2 confers resistance by decreasing intracellular DOX accumulation, which piR-39980 restores. This study reveals that piR-39980 could reduce fibrosarcoma resistance to DOX by modulating RRM2 and CYP1A2, implying that piRNA can be used in combination with DOX.
  • Restoration of microRNA-197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN
    Neha Jain, Basudeb Das, Bibekanand Mallick
    IUBMB Life, 2020
    MicroRNAs (miRNAs) act as crucial regulators of biological pathways/processes by reinforcing transcriptional programs and moderating transcripts. Emerging evidences have shown the involvement of dysregulated miRNAs in pathophysiology of human diseases including several cancer types. Recently, miR‐197‐3p has been reported to play different roles in different cancers; however, its role in fibrosarcoma, a highly aggressive and malignant soft tissue sarcoma originated from the mesenchymal tissues, has not yet been studied. Therefore, this study aims to investigate the possible regulatory roles of miR‐197‐3p in the oncogenicity of fibrosarcoma. For this, we initially performed qRT‐PCR of miR‐197‐3p, which we found to be downregulated in HT1080 human fibrosarcoma cells compared with IMR90‐tert normal fibroblast cells. Subsequently, we performed gain‐of‐function study by employing several methods such as MTT assay, clonogenic assay, wound healing, flow cytometry cell cycle analysis, and acridine orange staining after transfecting HT1080 cells with miR‐197‐3p mimic. From these assays, we observed that miR‐197‐3p significantly inhibits viability, colony forming, and migration ability as well as triggers G2/M phase cell cycle arrest and autophagy in fibrosarcoma cells. To understand the mechanism through which miRNA performs these functions, we predicted its targets using TargetScan and performed pathway enrichment analysis after screening them by their expression in fibrosarcoma. Among the enriched targets, we found RAN (ras‐related nuclear protein) to be a crucial target through which miR‐197‐3p represses tumorigenesis by binding to its 3´ UTR, validated by luciferase reporter assay. The tumor suppressive role of the miRNA was further confirmed by transfecting its mimic in RAN‐overexpressed cells which showed significant attenuation in tumorigenic effect of RAN in fibrosarcoma as seen in different assays. Taken together, our study unveiled that miR‐197‐3p acts as an oncosuppressor in fibrosarcoma through G2/M phase arrest and induction of autophagy, and raises the possibility to act as a novel therapeutic intervention for the malignancy.
  • piR-39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma
    Basudeb Das, Neha Jain, Bibekanand Mallick
    Biology of the Cell, 2020
    Piwi‐interacting RNAs (piRNAs) are a novel class of ∼23–36 nts long endogenous small non‐coding RNAs, earlier known to maintain germline genome integrity during development by regulating transposable elements. Recently, piRNAs are known to regulate cell proliferation, apoptosis and metastasis in different cancer cells. However, piRNAs have not yet been reported in human osteosarcoma (OS), a highly metastatic aggressive bone tumour among adolescents. Therefore, our current study aimed to decrypt the potential role of a piRNA, piR‐39980 in osteosarcoma, which was earlier reported by us in fibrosarcoma, neuroblastoma and epithelial ovarian cancer.
  • PIWI-interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells
    Jyoti Roy, Basudeb Das, Neha Jain, Bibekanand Mallick
    Journal of Cellular Physiology, 2020
    Neuroblastoma (NB) is the leading pediatric cancer known for its heterogeneity and clinical aggressiveness leading to chemoresistance. Recent evidence in small RNA research has led to the discovery of PIWI‐interacting RNAs (piRNAs) which work in an orchestrated fashion to modulate gene expression both in homeostatic conditions and abnormalities like cancer including NB. This study aims to decipher the possible role of a repeat‐derived piRNA, piR‐39980 (identified from our previous piRNA profiling study in human NB cell lines) in tumorigenesis of NB cells. piR‐39980, overexpressed in NB cells act as an oncopiR and promotes tumor progression, while its inhibition resulted in reduced viability, invasion as well as the migration of IMR‐32 cells. Interestingly, we observed that inhibition of piRNA induces senescence of NB cells without affecting the classical apoptosis pathway by modulating the expression of JAK3 through target binding. In addition, piR‐39980 was found to desensitize the effect of doxorubicin and inhibit drug‐induced apoptosis. Overall, we report piR‐39980, as the first oncopiR which might serve as a novel therapeutic target for this malignancy.
  • miR-197-5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101
    Neha Jain, Jyoti Roy, Basudeb Das, Bibekanand Mallick
    Molecular Carcinogenesis, 2019
    The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR‐197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR‐197‐5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90‐tert fibroblast cells. The transient overexpression of miR‐197‐5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration‐ and time‐dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR‐197‐5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorage‐independent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen‐associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR‐197‐5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA‐based therapeutic strategies for the cure of this malignancy.
  • Tumor suppressive activity of PIWI-interacting RNA in human fibrosarcoma mediated through repression of RRM2
    Basudeb Das, Jyoti Roy, Neha Jain, Bibekanand Mallick
    Molecular Carcinogenesis, 2019
  • Preferential binding to zinc oxide nanoparticle interface inhibits lysozyme fibrillation and cytotoxicity
    Kanti K. Yadav, Manoranjan Arakha, Basudeb Das, Bibekanand Mallick, Suman Jha
    International Journal of Biological Macromolecules, 2018

RECENT SCHOLAR PUBLICATIONS

  • Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumorexplants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways
    SK Nandi, A Pradhan, B Das, B Das, S Basu, B Mallick, A Dutta, ...
    Pathology-Research and Practice, 154029 , 2022
    2022
    Citations: 15
  • HIWI2 induces G2/M cell cycle arrest and apoptosis in human fibrosarcoma via the ROS/DNA damage/p53 axis
    B Das, S Sahoo, B Mallick
    Life Sciences 293, 120353 , 2022
    2022
    Citations: 23
  • Ribonucleotide reductase subunit M2 is a potential prognostic marker and therapeutic target for soft tissue sarcoma
    B Das, N Jain, B Mallick
    Gene 808, 145988 , 2022
    2022
    Citations: 10
  • Identification of potential Therapeutic Targets and Investigating Piwi-interacting RNA (piRNA) Mediated Target Regulations Implicated in Oncogenesis and Drug Resistance of Sarcoma
    B Das
    2022
  • miR-197-5p increases Doxorubicin-mediated anticancer cytotoxicity of HT1080 fibrosarcoma cells by decreasing drug efflux
    N Jain, B Das, B Mallick
    DNA repair 109, 103259 , 2022
    2022
    Citations: 21
  • piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair
    B Das, N Jain, B Mallick
    Communications Biology 4 (1), 1312 , 2021
    2021
    Citations: 45
  • Restoration of microRNA‐197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN
    N Jain, B Das, B Mallick
    IUBMB life 72 (5), 1034-1044 , 2020
    2020
    Citations: 20
  • piR‐39980 promotes cell proliferation, migration, invasion and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma
    B Das, N Jain, B Mallick
    Biology of the Cell 112 (3), 73-91 , 2019
    2019
    Citations: 42
  • PIWI‐interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells
    J Roy, B Das, N Jain, B Mallick
    Journal of cellular physiology 235 (3), 2286-2299 , 2019
    2019
    Citations: 37
  • miR‐197‐5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101
    N Jain, J Roy, B Das, B Mallick
    Molecular carcinogenesis 58 (8), 1376-1388 , 2019
    2019
    Citations: 31
  • Tumor suppressive activity of PIWI‐interacting RNA in human fibrosarcoma mediated through repression of RRM2
    B Das, J Roy, N Jain, B Mallick
    Molecular carcinogenesis 58 (3), 344-357 , 2019
    2019
    Citations: 56
  • Small RNA proteome as disease biomarker: An incognito treasure of clinical utility
    J Roy, N Jain, G Singh, B Das, B Mallick
    AGO-Driven Non-Coding RNAs, 101-136 , 2019
    2019
    Citations: 22
  • Preferential binding to zinc oxide nanoparticle interface inhibits lysozyme fibrillation and cytotoxicity
    KK Yadav, M Arakha, B Das, B Mallick, S Jha
    International journal of biological macromolecules 116, 955-965 , 2018
    2018
    Citations: 22

MOST CITED SCHOLAR PUBLICATIONS

  • Tumor suppressive activity of PIWI‐interacting RNA in human fibrosarcoma mediated through repression of RRM2
    B Das, J Roy, N Jain, B Mallick
    Molecular carcinogenesis 58 (3), 344-357 , 2019
    2019
    Citations: 56
  • piR-39980 mediates doxorubicin resistance in fibrosarcoma by regulating drug accumulation and DNA repair
    B Das, N Jain, B Mallick
    Communications Biology 4 (1), 1312 , 2021
    2021
    Citations: 45
  • piR‐39980 promotes cell proliferation, migration, invasion and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma
    B Das, N Jain, B Mallick
    Biology of the Cell 112 (3), 73-91 , 2019
    2019
    Citations: 42
  • PIWI‐interacting RNA 39980 promotes tumor progression and reduces drug sensitivity in neuroblastoma cells
    J Roy, B Das, N Jain, B Mallick
    Journal of cellular physiology 235 (3), 2286-2299 , 2019
    2019
    Citations: 37
  • miR‐197‐5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101
    N Jain, J Roy, B Das, B Mallick
    Molecular carcinogenesis 58 (8), 1376-1388 , 2019
    2019
    Citations: 31
  • HIWI2 induces G2/M cell cycle arrest and apoptosis in human fibrosarcoma via the ROS/DNA damage/p53 axis
    B Das, S Sahoo, B Mallick
    Life Sciences 293, 120353 , 2022
    2022
    Citations: 23
  • Small RNA proteome as disease biomarker: An incognito treasure of clinical utility
    J Roy, N Jain, G Singh, B Das, B Mallick
    AGO-Driven Non-Coding RNAs, 101-136 , 2019
    2019
    Citations: 22
  • Preferential binding to zinc oxide nanoparticle interface inhibits lysozyme fibrillation and cytotoxicity
    KK Yadav, M Arakha, B Das, B Mallick, S Jha
    International journal of biological macromolecules 116, 955-965 , 2018
    2018
    Citations: 22
  • miR-197-5p increases Doxorubicin-mediated anticancer cytotoxicity of HT1080 fibrosarcoma cells by decreasing drug efflux
    N Jain, B Das, B Mallick
    DNA repair 109, 103259 , 2022
    2022
    Citations: 21
  • Restoration of microRNA‐197 expression suppresses oncogenicity in fibrosarcoma through negative regulation of RAN
    N Jain, B Das, B Mallick
    IUBMB life 72 (5), 1034-1044 , 2020
    2020
    Citations: 20
  • Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumorexplants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways
    SK Nandi, A Pradhan, B Das, B Das, S Basu, B Mallick, A Dutta, ...
    Pathology-Research and Practice, 154029 , 2022
    2022
    Citations: 15
  • Ribonucleotide reductase subunit M2 is a potential prognostic marker and therapeutic target for soft tissue sarcoma
    B Das, N Jain, B Mallick
    Gene 808, 145988 , 2022
    2022
    Citations: 10
  • Identification of potential Therapeutic Targets and Investigating Piwi-interacting RNA (piRNA) Mediated Target Regulations Implicated in Oncogenesis and Drug Resistance of Sarcoma
    B Das
    2022