{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:04:44Z","timestamp":1785769484871,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2017YFA0505103"],"award-info":[{"award-number":["2017YFA0505103"]}]},{"DOI":"10.13039\/501100001809","name":"NSFC","doi-asserted-by":"publisher","award":["21877068"],"award-info":[{"award-number":["21877068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Chinese Ministry of Science and Technology","award":["2020YFC2002705"],"award-info":[{"award-number":["2020YFC2002705"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carbonic anhydrase IX (CA9), a pH-regulating transmembrane protein, is highly expressed in solid tumors, and particularly in clear cell renal cell carcinoma (ccRCC). The catalytic mechanisms of CA9 are well defined, but its roles in mediating cell migration\/invasion and survival in ccRCC remain to be determined. Here, we confirmed that the mRNA expression of CA9 in ccRCC was significantly higher than that in para-carcinoma tissues from analysis of the datasets in The Cancer Genome Atlas. CA9 knockdown upregulated oxidative phosphorylation-associated proteins and increased mitochondrial biogenesis, resulting in the reversal of the Warburg phenotype and the inhibition of cell growth. Our study revealed that CA9 knockdown upregulated mitochondrial arginase 2 (ARG2), leading to the accumulation of putrescine, which suppressed ccRCC proliferation. Surfaceomics analysis revealed that CA9 knockdown downregulated proteins associated with extracellular matrix (ECM)\u2014receptor interaction and cell adhesion, resulting in decreased cell migration. CA9 silencing also downregulated amino acid transporters, leading to reduced cellular amino acids. Collectively, our data show that CA9 knockdown suppresses proliferation via metabolic reprogramming and reduced cell migration, reaffirming that CA9 is a potential therapeutic target for ccRCC treatment.<\/jats:p>","DOI":"10.3390\/ijms21165939","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T09:22:31Z","timestamp":1597828951000},"page":"5939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["CA9 Silencing Promotes Mitochondrial Biogenesis, Increases Putrescine Toxicity and Decreases Cell Motility to Suppress ccRCC Progression"],"prefix":"10.3390","volume":"21","author":[{"given":"Jiatong","family":"Xu","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Xu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Ding","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100043, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-1280","authenticated-orcid":false,"given":"Haiteng","family":"Deng","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48615","DOI":"10.1074\/jbc.R100045200","article-title":"Carbonic anhydrase: New insights for an ancient enzyme","volume":"276","author":"Tripp","year":"2001","journal-title":"J. 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