{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:36:42Z","timestamp":1774928202068,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007113","name":"Arak University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007113","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>An anticancer drug known as Rapamycin acts by inhibiting the mammalian target of the Rapamycin pathway. This agent has recently been investigated for its potential therapeutic benefits in sensitizing drug\u2010resistant breast cancer (BC) treatment. The molecular mechanism underlying these effects, however, is still a mystery. Using a systems biology method and in vitro experiment, this study sought to discover essential genes and microRNAs (miRNAs) targeted by Rapamycin in triple\u2010negative BC (TNBC) cells to aid prospective new medications with less adverse effects in BC treatment. We developed the transcription factor\u2010miRNA\u2010gene and protein\u2212protein interaction networks using the freely accessible microarray data sets. FANMOD and MCODE were utilized to identify critical regulatory motifs, clusters, and seeds. Then, functional enrichment analyses were conducted. Using topological analysis and motif detection, the most important genes and miRNAs were discovered. We used quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) to examine the effect of Rapamycin on the expression of the selected genes and miRNAs to verify our findings. We performed flow cytometry to investigate Rapamycin's impact on cell cycle and apoptosis. Furthermore, wound healing and migration assays were done. Three downregulated (PTGS2, EGFR, VEGFA) and three upregulated (c\u2010MYC, MAPK1, PIK3R1) genes were chosen as candidates for additional experimental verification. There were also three upregulated miRNAs (miR\u201092a, miR\u201016, miR\u201020a) and three downregulated miRNAs (miR\u2010146a, miR\u2010145, miR\u201027a) among the six selected miRNAs. The qRT\u2010PCR findings in MDA\u2010MB\u2010231 cells indicated that c\u2010MYC, MAPK1, PIK3R1, miR\u201092a, miR\u201016, and miR\u201020a expression levels were considerably elevated following Rapamycin treatment, whereas PTGS2, EGFR, VEGFA, miR\u2010146a, and miR\u2010145 expression levels were dramatically lowered (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). These genes are engaged in cancer pathways, transcriptional dysregulation in cancer, and cell cycle, according to the top pathway enrichment findings. Migration and wound healing abilities of the cells declined after Rapamycin treatment, and the number of apoptotic cells increased. We demonstrated that Rapamycin suppresses cell migration and metastasis in the TNBC cell line. In addition, our data indicated that Rapamycin induces apoptosis in this cell line. The discovered vital genes and miRNAs affected by Rapamycin are anticipated to have crucial roles in the pathogenesis of TNBC and its therapeutic resistance.<\/jats:p>","DOI":"10.1002\/mc.23628","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T08:32:20Z","timestamp":1696408340000},"page":"1960-1973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A systems biology approach and in vitro experiment indicated Rapamycin targets key cancer and cell cycle\u2010related genes and miRNAs in triple\u2010negative breast cancer cells"],"prefix":"10.1002","volume":"62","author":[{"given":"Ali","family":"Tafti","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Molecular Medicine Faculty of Medicine, Arak University of Medical Sciences Arak 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