{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:29:21Z","timestamp":1790886561537,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2320-B-006-041-MY3"],"award-info":[{"award-number":["MOST 108-2320-B-006-041-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2320-B-006-059-"],"award-info":[{"award-number":["MOST 110-2320-B-006-059-"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2811-B-006-549-"],"award-info":[{"award-number":["MOST 110-2811-B-006-549-"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2622-B-002 -010"],"award-info":[{"award-number":["MOST 109-2622-B-002 -010"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 110-2622-B-002 -002"],"award-info":[{"award-number":["MOST 110-2622-B-002 -002"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Surgery, National Taiwan University Hospital, Taiwan","award":["109-S4624"],"award-info":[{"award-number":["109-S4624"]}]},{"name":"Department of Surgical Oncology, National Taiwan University Cancer Center, Taiwan","award":["NTUCCS-110-09"],"award-info":[{"award-number":["NTUCCS-110-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TAR (HIV-1) RNA binding protein 2 (TARBP2) is an RNA-binding protein participating in cytoplasmic microRNA processing. Emerging evidence has shown the oncogenic role of TARBP2 in promoting cancer progression, making it an unfavorable prognosis marker for breast cancer. Hypoxia is a hallmark of the tumor microenvironment which induces hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) for transcriptional regulation. HIF-1\u03b1 is prone to be rapidly destabilized by the ubiquitination\u2013proteasomal degradation system. In this study, we found that TARBP2 expression is significantly correlated with induced hypoxia signatures in human breast cancer tissues. At a cellular level, HIF-1\u03b1 protein level was maintained by TARBP2 under either normoxia or hypoxia. Mechanistically, TARBP2 enhanced HIF-1\u03b1 protein stability through preventing its proteasomal degradation. In addition, downregulation of multiple E3 ligases targeting HIF-1\u03b1 (VHL, FBXW7, TRAF6) and reduced ubiquitination of HIF-1\u03b1 were also induced by TARBP2. In support of our clinical findings that TARBP2 is correlated with tumor hypoxia, our IHC staining showed the positive correlation between HIF-1\u03b1 and TARBP2 in human breast cancer tissues. Taken together, this study indicates the regulatory role of TARBP2 in the ubiquitination\u2013proteasomal degradation of HIF-1\u03b1 protein in breast cancer.<\/jats:p>","DOI":"10.3390\/ijms23010208","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1\u03b1 in Breast Cancer"],"prefix":"10.3390","volume":"23","author":[{"given":"Jie-Ning","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-1467","authenticated-orcid":false,"given":"Pai-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5591-0288","authenticated-orcid":false,"given":"Ching-Feng","family":"Chiu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jhen","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-0138","authenticated-orcid":false,"given":"Li-Wei","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan"},{"name":"Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan"},{"name":"Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100405","DOI":"10.1016\/j.genrep.2019.100405","article-title":"The role of HIF-1 alpha, CBP and p300 in the regulation of Nav1.5 expression in breast cancer cells","volume":"16","author":"Dewadas","year":"2019","journal-title":"Gene Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10695-018-0597-7","article-title":"Molecular characterization and expression regulation of the factor-inhibiting HIF-1 (FIH-1) gene under hypoxic stress in bighead carp (Aristichthys nobilis)","volume":"45","author":"Feng","year":"2019","journal-title":"Fish Physiol. 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