{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T18:36:20Z","timestamp":1768502180917,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,24]]},"group-title":"Cancer Biology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Prognosis of children with high-risk hepatoblastoma (HB), the most common pediatric liver cancer, remains poor. In this study, we found ribonucleotide reductase (RNR) subunit M2 (\n                  <jats:italic>RRM2<\/jats:italic>\n                  ) was one of the key genes supporting cell proliferation in high-risk HB. While standard chemotherapies could effectively suppress RRM2 in HB cells, they induced a significant upregulation of the other RNR M2 subunit,\n                  <jats:underline>RRM2B<\/jats:underline>\n                  . Computational analysis revealed distinct signaling networks RRM2 and\n                  <jats:underline>RRM2B<\/jats:underline>\n                  were involved in HB patient tumors, with RRM2 supporting cell proliferation and\n                  <jats:underline>RRM2B<\/jats:underline>\n                  participating heavily in stress response pathways. Indeed,\n                  <jats:underline>RRM2B<\/jats:underline>\n                  upregulation in chemotherapy-treated HB cells promoted cell survival and subsequent relapse, during which\n                  <jats:underline>RRM2B<\/jats:underline>\n                  was gradually replaced back by RRM2. Combining an RRM2 inhibitor with chemotherapy showed an effective delaying of HB tumor relapse in vivo. Overall, our study revealed the distinct roles of the two RNR M2 subunits and their dynamic switching during HB cell proliferation and stress response.\n                <\/jats:p>","DOI":"10.1101\/2023.01.24.525404","type":"posted-content","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:25:27Z","timestamp":1674606327000},"source":"Crossref","is-referenced-by-count":0,"title":["Ribonucleotide Reductase Subunit Switching in Hepatoblastoma Drug Response and Relapse"],"prefix":"10.64898","author":[{"given":"Anthony","family":"Brown","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Indersie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolai","family":"Timchenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baranda S.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meifen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junmin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shondra M.","family":"Pruett-Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-4429","authenticated-orcid":false,"given":"Jiyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cairo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-150X","authenticated-orcid":false,"given":"Liqin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023012614000976000_2023.01.24.525404v1.1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/hpb.12112","article-title":"Predictors of survival and incidence of hepatoblastoma in the paediatric population","volume":"15","year":"2013","journal-title":"Hpb"},{"key":"2023012614000976000_2023.01.24.525404v1.2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2008-0011"},{"key":"2023012614000976000_2023.01.24.525404v1.3","doi-asserted-by":"crossref","first-page":"pkz007","DOI":"10.1093\/jncics\/pkz007","article-title":"Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988-2012","volume":"3","year":"2019","journal-title":"JNCI Cancer Spectr"},{"key":"2023012614000976000_2023.01.24.525404v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30598-8"},{"key":"2023012614000976000_2023.01.24.525404v1.5","doi-asserted-by":"crossref","unstructured":"Bell CC , Gilan O. 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