{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T19:55:49Z","timestamp":1767729349282,"version":"build-2238731810"},"reference-count":31,"publisher":"Portland Press Ltd.","issue":"4","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":720,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8,31]]},"abstract":"<jats:p>The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 \u03b1 (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA\u2013Gadd45a, and miR-374 inhibitors + siRNA\u2013Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA\u2013Gadd45a group showed decreased miR-374 level; the siRNA\u2013Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.<\/jats:p>","DOI":"10.1042\/bsr20170710","type":"journal-article","created":{"date-parts":[[2017,7,5]],"date-time":"2017-07-05T20:10:45Z","timestamp":1499285445000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway"],"prefix":"10.1042","volume":"37","author":[{"given":"Xiao-Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiu-Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Guo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Hebei Engineering University, Handan 056002, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2017,8,4]]},"reference":[{"key":"2021111618512356700_B1","doi-asserted-by":"crossref","first-page":"e95337","DOI":"10.1371\/journal.pone.0095337","article-title":"Imiquimod induces apoptosis of squamous cell carcinoma (SCC) cells via regulation of A20","volume":"9","author":"Sohn","year":"2014","journal-title":"PLoS One"},{"key":"2021111618512356700_B2","doi-asserted-by":"crossref","first-page":"34081","DOI":"10.1038\/srep34081","article-title":"Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process","volume":"6","author":"Warren","year":"2016","journal-title":"Sci. Rep."},{"key":"2021111618512356700_B3","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1053\/j.semdp.2014.12.017","article-title":"Pathological factors, behavior, and histological prognostic risk groups in subtypes of penile squamous cell carcinomas (SCC)","volume":"32","author":"Sanchez","year":"2015","journal-title":"Semin. Diagn. Pathol."},{"key":"2021111618512356700_B4","doi-asserted-by":"crossref","first-page":"7425","DOI":"10.1073\/pnas.1012670108","article-title":"Defining the origins of Ras\/p53-mediated squamous cell carcinoma","volume":"108","author":"White","year":"2011","journal-title":"Proc. Natl. Acad. Sci. 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Ther."},{"key":"2021111618512356700_B8","doi-asserted-by":"crossref","first-page":"41083","DOI":"10.1074\/jbc.M111.258715","article-title":"GADD45A protein plays an essential role in active DNA demethylation during terminal osteogenic differentiation of adipose-derived mesenchymal stem cells","volume":"286","author":"Zhang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2021111618512356700_B9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1517\/14728222.2011.643299","article-title":"Targeting the p53 signaling pathway in cancer therapy - the promises, challenges and perils","volume":"16","author":"Stegh","year":"2012","journal-title":"Expert Opin. Ther. 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