{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:33:17Z","timestamp":1753878797210,"version":"3.41.2"},"reference-count":48,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T00:00:00Z","timestamp":1722729600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82002771","NSFC81773391","NSFC81702530"],"award-info":[{"award-number":["NSFC82002771","NSFC81773391","NSFC81702530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lung cancer remains the leading cause of cancer\u2010related deaths, with cigarette smoking being the most critical factor, linked to nearly 90% of lung cancer cases. NNK, a highly carcinogenic nitrosamine found in tobacco, is implicated in the lung cancer\u2010causing effects of cigarette smoke. Although NNK is known to mutate or activate certain oncogenes, its potential interaction with p27 in modulating these carcinogenic effects is currently unexplored. Recent studies have identified specific downregulation of p27 in human squamous cell carcinoma, in contrast to adenocarcinoma. Additionally, exposure to NNK significantly suppresses p27 expression in human bronchial epithelial cells. Subsequent studies indicates that the downregulation of p27 is pivotal in NNK\u2010induced cell transformation. Mechanistic investigations have shown that reduced p27 expression leads to increased level of ITCH, which facilitates the degradation of Jun B protein. This degradation in turn, augments miR\u2010494 expression and its direct regulation of JAK1 mRNA stability and protein expression, ultimately activating STAT3 and driving cell transformation. In summary, our findings reveal that: (1) the downregulation of p27 increases Jun B expression by upregulating Jun B E3 ligase ITCH, which then boosts miR\u2010494 transcription; (2) Elevated miR\u2010494 directly binds to 3\u2032\u2010UTR of JAK1 mRNA, enhancing its stability and protein expression; and (3) The JAK1\/STAT3 pathway is a downstream effector of p27, mediating the oncogenic effect of NNK in lung cancer. These findings provide significant insight into understanding the participation of mechanisms underlying p27 inhibition of NNK induced lung squamous cell carcinogenic effect.<\/jats:p>","DOI":"10.1111\/jcmm.18577","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T03:39:58Z","timestamp":1722829198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["p27 specifically decreases in squamous carcinoma, and mediates <scp>NNK<\/scp>\u2010induced transformation of human bronchial epithelial cells"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-2838","authenticated-orcid":false,"given":"Minggang","family":"Peng","sequence":"first","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Meng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengda","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Qian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruifan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglei","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanshu","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health)  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27816"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34160-w"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30958-8"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncponc1187"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx980005y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2013.09.012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005176"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2010.03.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1586254"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes5040865"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00045-5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.470"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.119.018440"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071545"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-017-1161-7"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.148130"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.496"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2016.1196313"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-12-0922"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.05.022"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4285"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.05.019"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-309"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2017.00071"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2015.02.006"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2018.12.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2004.09.001"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12301"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2661"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2190"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3757"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2734"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206479"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/21623996.2014.999503"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0374-1"},{"issue":"3","key":"e_1_2_10_38_1","first-page":"3075","article-title":"miR\u2010494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression","volume":"15","author":"Cheng L","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000495867"},{"issue":"8","key":"e_1_2_10_40_1","first-page":"1507","article-title":"Increased expression of miR\u2010494 in serum of patients with prostate cancer and its potential diagnostic value","volume":"65","author":"Cai B","year":"2019","journal-title":"Clin Lab"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.6265"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4527"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2019.05.007"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13933"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3416-0"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-3516"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.91"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni763"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510664103"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.18577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T11:55:03Z","timestamp":1723636503000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.18577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":48,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/jcmm.18577"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.18577","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"type":"print","value":"1582-1838"},{"type":"electronic","value":"1582-4934"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2023-09-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e18577"}}