{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:19:58Z","timestamp":1789384798678,"version":"build-2803163510"},"reference-count":37,"publisher":"Baishideng Publishing Group Inc.","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Stem Cells"],"abstract":"BACKGROUND<\/jats:p>\n Cervical cancer (CC) stem cell-like cells (CCSLCs), defined by the capacity of differentiation and self-renewal and proliferation, play a significant role in the progression of CC. However, the molecular mechanisms regulating their self-renewal are poorly understood. Therefore, elucidation of the epigenetic mechanisms that drive cancer stem cell self-renewal will enhance our ability to improve the effectiveness of targeted therapies for cancer stem cells.<\/jats:p>\n AIM<\/jats:p>\n To explore how DNA methyltransferase 1 (DNMT1)\/miR-342-3p\/Forkhead box M1 (FoxM1), which have been shown to have abnormal expression in CCSLCs, and their signaling pathways could stimulate self-renewal-related stemness in CCSLCs.<\/jats:p>\n METHODS<\/jats:p>\n Sphere-forming cells derived from CC cell lines HeLa, SiHa and CaSki served as CCSLCs. Self-renewal-related stemness was identified by determining sphere and colony formation efficiency, CD133 and CD49f protein level, and SRY-box transcription factor 2 and octamer-binding transcription factor 4 mRNA level. The microRNA expression profiles between HeLa cells and HeLa-derived CCSLCs or mRNA expression profiles that HeLa-derived CCSLCs were transfected with or without miR-342-3p mimic were compared using quantitative PCR analysis. The expression levels of DNMT1 mRNA, miR-342-3p, and FoxM1 protein were examined by quantitative real-time PCR and western blotting. In vivo carcinogenicity was assessed using a mouse xenograft model. The functional effects of the DNMT1\/miR-342-3p\/FoxM1 axis were examined by in vivo and in vitro gain-of-activity and loss-of-activity assessments. Interplay among DNMT1, miR-342-3p, and FoxM1 was tested by methylation-specific PCR and a respective luciferase reporter assay.<\/jats:p>\n RESULTS<\/jats:p>\n CCSLCs derived from the established HeLa cell lines displayed higher self-renewal-related stemness, including enhanced sphere and colony formation efficiency, increased CD133 and CD49f protein level, and heightened transcriptional quantity of stemness-related factors SRY-box transcription factor 2 and octamer-binding transcription factor 4 in vitro as well as a stronger tumorigenic potential in vivo compared to their parental cells. Moreover, quantitative PCR showed that the miR-342-3p level was downregulated in HeLa-derived CCSLCs compared to HeLa cells. Its mimic significantly decreased DNMT1 and FoxM1 mRNA expression levels in CCSLCs. Knockdown of DNMT1 or miR-342-3p mimic transfection suppressed DNMT1 expression, increased miR-342-3p quantity by promoter demethylation, and inhibited CCSLC self-renewal. Inhibition of FoxM1 by shRNA transfection also resulted in the attenuation of CCSLC self-renewal but had little effect on the DNMT1 activity and miR-342-3p expression. Furthermore, the loss of CCSLC self-renewal exerted by miR-342-3p mimic was inverted by the overexpression of DNMT1 or FoxM1. Furthermore, DNMT1 and FoxM1 were recognized as straight targets by miR-342-3p in HeLa-derived CCSLCs.<\/jats:p>\n CONCLUSION<\/jats:p>\n Our findings suggested that a novel DNMT1\/miR-342-3p\/FoxM1 signal axis promotes CCSLC self-renewal and presented a potential target for the treatment of CC through suppression of CCSLC self-renewal. However, this pathway has been previously implicated in CC, as evidenced by prior studies showing miR-342-3p-mediated downregulation of FoxM1 in cervical cancer cells. Additionally, research on liver cancer further supports the involvement of miR-342-3p in suppressing FoxM1 expression. While our study contributed to this body of knowledge, we did not present a completely novel axis but reinforced the therapeutic potential of targeting the DNMT1\/miR-342-3p\/FoxM1 axis to suppress CCSLC self-renewal in CC treatment.<\/jats:p>","DOI":"10.4252\/wjsc.v17.i3.99472","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T09:40:27Z","timestamp":1742377227000},"source":"Crossref","is-referenced-by-count":3,"title":["DNA methyltransferase 1\/miR-342-3p\/Forkhead box M1 signaling axis promotes self-renewal in cervical cancer stem-like cells in vitro<\/i> and nude mice models"],"prefix":"10.4252","volume":"17","author":[{"given":"Xiao-Zheng","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Li","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Bei","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Zhi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Xia","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Qiang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-024-18858-3"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32470-X"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1232"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3597"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23095167"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00611-y"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2020.188491"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-021-01521-7"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.07.039"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.07.020"},{"key":"B12","unstructured":"Tao K, Yang J, Guo Z, Hu Y, Sheng H, Gao H, Yu H. 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