{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:54:36Z","timestamp":1792079676588,"version":"4.4.0"},"reference-count":108,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional funds and generous donations from our patients"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Huntingtin-interacting protein 1-related (HIP1R) shares some function similarities with HIP1, and HIP1 regulates arthritis and RA fibroblast-like synoviocytes (FLS) invasiveness. Therefore, we hypothesized that HIP1R might be involved in the regulation of FLS phenotypes and molecular processes relevant to RA. siRNA was used to knockdown HIP1R, HIP1 or control in RA FLS, followed by cell studies for invasion in Matrigel, migration, proliferation, and adhesion. RNA was sequenced and analyzed. HIP1R knockdown significantly reduced RA FLS invasiveness and migration (p &lt; 0.05). The DEGs in siRNA HIP1R had an enrichment for GO processes \u201castrocyte and glial cell projection\u201d, \u201csmall GTPase signaling\u201d, and \u201cPDGFR signaling\u201d. The most significantly DEGs had decreased expression in siRNA HIP1R and included AKT1S1, GABBR2, GPR56, and TXNDC12. siRNA HIP1 RA FLS had an enrichment for the \u201cRap1 signaling pathway\u201d and \u201cGrowth factor receptor binding\u201d. The most significantly DEGs in HIP1 siRNA included FGF2, PGF, and SLC39A8. HIP1R and HIP1 DEG lists had a greater than expected number of similar genes (p = 0.0015), suggesting that, despite the major differences detected, both have partially overlapping functions in RA FLS. The most significantly DEGs in both HIP1R and HIP1 analyses are involved in cancer cell behaviors and outcomes. HIP1R is a new gene implicated in RA FLS invasiveness and migration, and regulates unique pathways and cell processes relevant to both RA as well as cancer biology. Our study provides new insight into processes implicated in FLS invasiveness, which is relevant for joint damage in RA, and identify new potential gene targets for FLS-specific treatments.<\/jats:p>","DOI":"10.3390\/cells14070483","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T13:48:20Z","timestamp":1742824100000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Huntingtin-Interacting Protein 1-Related (HIP1R) Regulates Rheumatoid Arthritis Synovial Fibroblast Invasiveness"],"prefix":"10.3390","volume":"14","author":[{"given":"Teresina","family":"Laragione","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Percio S.","family":"Gulko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,23]]},"reference":[{"key":"ref_1","first-page":"31","article-title":"Prognostic factors in rheumatoid arthritis","volume":"44","author":"Breedveld","year":"1996","journal-title":"J. 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