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Multimerin 1 aids in the progression of ovarian cancer possibly via modulation of DNA damage response and repair pathways

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Abstract

Ovarian cancer is one of the leading causes of deaths among women. Despite advances in the treatment regimes, a high rate of diagnosis in the advanced stage makes it almost an incurable malignancy. Thus, more research efforts are required to identify potential molecular markers for early detection of the disease and therapeutic targets to augment the survival rate of ovarian cancer patients. Previously, in this context, we identified dysregulated expression of multimerin 1 (MMRN1) in ovarian cancer. To elucidate the relationship between MMRN1 expression and ovarian cancer progression, siRNA-based MMRN1 knockdown was employed and various cell assays were performed to study its effect on ovarian cancer cells. In addition, network of dysregulated proteins was identified by quantitative proteomics and associated pathways were explored by bioinformatics analysis. MMRN1 silencing showed a significant reduction in cell viability, adhesion, migration, and invasion and a high frequency of cell apoptosis. Label-free quantitative proteomics and in-depth statistical analysis identified 448 dysregulated proteins, majority of which were overexpressed in MMRN1 knockdown cells. The pathways overrepresented in ovarian cancer were DNA replication, mismatch repair, nucleotide excision repair, and cell cycle regulation. Conclusively, the findings of this study suggest that MMRN1 aids in the progression of ovarian cancer via modulation of DNA damage response and repair pathways.

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Acknowledgements

VK and AS thank SERB and Council of Scientific and Industrial Research (CSIR), Govt. of India for their fellowships, respectively.

Funding

This work was supported by a research grant received from the Science and Engineering Research Board (SERB), Govt. of India (File No. CRG/2020/002194).

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Author notes

  1. Abhinav Saini and Vikrant Kumar have contributed equally to this work.

Authors and Affiliations

  1. Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 11029, India

    Abhinav Saini, Vikrant Kumar, Anil Kumar Tomar & Savita Yadav

  2. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 11029, India

    Alpana Sharma

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  1. Abhinav Saini
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  2. Vikrant Kumar
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Contributions

SY, AKT, VK, and AS conceptualized and designed the study. VK and AS performed the experiments. SY, AKT, VK, and AS analyzed the data. VK and AKT drafted the manuscript and all authors have reviewed and approved the final manuscript for submission.

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Correspondence to Savita Yadav.

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Supplementary Information

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11010_2023_4668_MOESM1_ESM.xlsx

Supplementary file1 (XLSX 38 KB)Supplementary file 1: Differentially expressed proteins selected by volcano plot (Thresholds, FC 2, and raw.pval 0.05). FC- Fold change; raw.pval- T test p-value. Columns: (A) Name of the DEP; (B) Uniprot accession; (C) FC; (D) log2 (FC); and (D) raw.pval 0.05.

11010_2023_4668_MOESM2_ESM.xlsx

Supplementary file2 (XLSX 28 KB)Supplementary file 2: Enrichment analysis of GO terms and KEGG pathways. Sheets: (1) Biological processes (BP); (2) Cellular component (CC); (3) Molecular functions (MF); and (4) KEGG pathways. FDR: false discovery rate. Each sheet contains 7 columns (A-G) providing following information—category (A), GO term/pathway name (B), count of proteins associated with the term (C), %age of proteins associated with the term (D), p-value (E), names of genes linked to proteins in the enriched terms (F), and false discovery rate (G).

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Saini, A., Kumar, V., Tomar, A.K. et al. Multimerin 1 aids in the progression of ovarian cancer possibly via modulation of DNA damage response and repair pathways. Mol Cell Biochem 478, 2395–2403 (2023). https://doi.org/10.1007/s11010-023-04668-5

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