{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:44:43Z","timestamp":1785840283472,"version":"3.56.0"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Renal cell carcinoma (RCC) is one of the highly malignant tumors in the world. Global Cancer Statistics 2020 estimated that there were 179,368 deaths from kidney tumors. Therefore, exploring the prognostic biomarkers of RCC is of great significance for RCC patients. This study aims to explore the potential mechanism and prognostic value of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene\u2010targeting co\u2010expression microRNAs in RCC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 60 RCC patients were included. Quantitative real\u2010time PCR (qRT\u2010PCR), western blotting, and immunohistochemistry were used for LHPP, microRNA\u2010765, microRNA\u201021, and microRNA\u2010144 levels evaluation. Cell Counting Kit\u20108 assay, dual\u2010luciferase reporter gene assay, invasion assay, and RNA fluorescence in situ hybridization were used for functional analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with adjacent tissues, LHPP levels in cancer tissues were significantly increased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). Herein, we confirmed that microRNA\u2010765, microRNA\u201021, and microRNA\u2010144 were direct biological targets of LHPP. MicroRNA\u2010765 (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.570, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), microRNA\u201021 (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.495, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001), and microRNA\u2010144 (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.463, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) expression levels were negatively correlated with LHPP expression levels. The high expression levels of microRNA\u2010765, microRNA\u201021, and microRNA\u2010144 in RCC tissues were associated with poor differentiation, recurrence, and poor prognosis (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). <jats:italic>In vitro<\/jats:italic>, microRNA\u2010765, microRNA\u201021, and microRNA\u2010144 act as oncogenes to promote proliferation, invasion, and epithelial\u2010mesenchymal transition (EMT) through targeting LHPP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MicroRNA\u2010765, microRNA\u201021, and microRNA\u2010144 are independent risk biomarkers for RCC patients. Inhibiting the expression levels of microRNA\u2010765, microRNA\u201021, and microRNA\u2010144 can reduce the proliferation, EMT, and invasion of RCC cells. Therefore, the above three microRNAs are expected to become molecular biomarkers for RCC therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24077","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T20:30:04Z","timestamp":1635280204000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Three LHPP gene\u2010targeting co\u2010expressed microRNAs (microRNA\u2010765, microRNA\u201021, and microRNA\u2010144) promote proliferation, epithelial\u2010mesenchymal transition, invasion, and are independent prognostic biomarkers in renal cell carcinomas patients"],"prefix":"10.1002","volume":"35","author":[{"given":"Kexin","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Nephrology The Second Affiliated Hospital, Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongda","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Second Affiliated Hospital, Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9673-0988","authenticated-orcid":false,"given":"Xiaoying","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Nephrology Beidahuang Industry Group General Hospital Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010020\u201001266\u20107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature26140"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20194142"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20182270"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmaa015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.099"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010020\u201001225\u20102"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.47239"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.08.006"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29969"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882\u2010018\u20100884\u20107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010020\u20101340\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28424"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010014\u20101976\u20108"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03415-2"}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.24077","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.24077","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.24077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:09:52Z","timestamp":1693192192000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.24077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":16,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/jcla.24077"],"URL":"https:\/\/doi.org\/10.1002\/jcla.24077","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"value":"0887-8013","type":"print"},{"value":"1098-2825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]},"assertion":[{"value":"2021-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24077"}}