{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:34:08Z","timestamp":1769092448951,"version":"3.49.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T00:00:00Z","timestamp":1652572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radioresistance remains a major clinical challenge in cervical cancer therapy and results in tumor relapse and metastasis. Nevertheless, the detailed mechanisms are still largely enigmatic. This study was conducted to elucidate the prospective impacts of microRNA-29a (miR-29a) on the modulation of radioresistance-associated cervical cancer progression. Herein, we established two pairs of parental wild-type (WT) and radioresistant (RR) cervical cancer cells (CaSki and C33A), and we found that constant suppressed miR-29a, but not miR-29b\/c, was exhibited in RR-clones that underwent a dose of 6-Gy radiation treatment. Remarkably, radioresistant clones displayed low radiosensitivity, and the reduced apoptosis rate resulted in augmented surviving fractions, measured by the clonogenic survival curve assay and the Annexin V\/Propidium Iodide apoptosis assay, respectively. Overexpression of miR-29a effectively intensified the radiosensitivity and triggered the cell apoptosis in RR-clones. In contrast, suppressed miR-29a modestly abridged the radiosensitivity and abolished the cell apoptosis in WT-clones. Hence, ectopically introduced miR-29a into RR-clones notably attenuated the wound-healing rate and cell migration, whereas reduced miR-29a aggravated cell mobilities of WT-clones estimated via the in vitro wound-healing assay and time-lapse recording assay. Notably, we further established the in vivo short-term lung locomotion metastasis model in BALB\/c nude mice, and we found that increased lung localization was shown after tail-vein injection of RR-CaSki cells compared to those of WT-CaSki cells. Amplified miR-29a significantly eliminated the radioresistance-enhanced lung locomotion. Our data provide evidence suggesting that miR-29a is a promising microRNA signature in radioresistance of cervical cancer cells and displays multifaceted innovative roles involved in anti-radioresistance, escalated apoptosis, and anti-cell migration\/metastasis. Amalgamation of a nucleoid-based strategy (miR-29a) together with conventional radiotherapy may be an innovative and eminent strategy to intensify the radiosensitivity and further protect against the subsequent radioresistance and the potential metastasis in cervical cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms23105524","type":"journal-article","created":{"date-parts":[[2022,5,15]],"date-time":"2022-05-15T09:48:22Z","timestamp":1652608102000},"page":"5524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["MicroRNA-29a Manifests Multifaceted Features to Intensify Radiosensitivity, Escalate Apoptosis, and Revoke Cell Migration for Palliating Radioresistance-Enhanced Cervical Cancer Progression"],"prefix":"10.3390","volume":"23","author":[{"given":"Pei-Chin","family":"Chuang","sequence":"first","affiliation":[{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"},{"name":"Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807017, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping-Tsung","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Chi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-5490","authenticated-orcid":false,"given":"Yen-Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"},{"name":"School of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eng-Yen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan"},{"name":"School of Traditional Chinese Medicine, Chang Gung University, Kaohsiung 833401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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