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In breast, ovarian, prostate, and lung cancers, reduced NEP levels are associated with cancer progression. In Glioblastoma (GBM), the level of NEP is downregulated. This study aims to understand the role and expression pattern of NEP in GBM. A web-based tool, UALCAN, was utilized to understand the expression pattern of NEP in GBM, followed by patient survival analysis using the Cancer Genome Atlas (TCGA) data. Further,\n                    <jats:italic>in-vitro<\/jats:italic>\n                    scratch assays were performed on U87 MG cells to understand the effect of NEP silencing, as well as its upregulation using certain HDAC1 inhibitors identified through\n                    <jats:italic>in-silico<\/jats:italic>\n                    studies (melphalan, tasimelteon and panobinostat), to study the cancer progression. The UALCAN web tool revealed that NEP levels are downregulated in GBM. Additionally, the\n                    <jats:italic>in-vitro<\/jats:italic>\n                    scratch assay demonstrated that silencing of NEP augmented cell proliferation, whereas the upregulation of NEP using the HDAC1 inhibitors resulted in decreased cancer proliferation. These results suggest an inverse correlation between the NEP levels and GBM proliferation. The tumor suppression exhibited by NEP could be attributed to its degradation of mitogenic proteins such as FGF-2, IGFs etc. In conclusion, NEP can be a promising biomarker and a drug target against GBM.\n                  <\/jats:p>","DOI":"10.1007\/s11010-025-05341-9","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T09:03:49Z","timestamp":1751187829000},"page":"5671-5683","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neprilysin regulates the progression of glioblastoma: an in-vitro study using siRNA mediated gene silencing and HDAC1 mediated upregulation of neprilysin in U87 MG cells"],"prefix":"10.1007","volume":"480","author":[{"given":"Adarsh","family":"Gopinathan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runali","family":"Sankhe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavendra","family":"Upadhya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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