Find in Library

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 <i>microRNA-29a</i> (<i>miR-29a</i>) 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 <i>miR-29a,</i> but not <i>miR-29b/c,</i> 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 <i>miR-29a</i> effectively intensified the radiosensitivity and triggered the cell apoptosis in RR-clones. In contrast, suppressed <i>miR-29a</i> modestly abridged the radiosensitivity and abolished the cell apoptosis in WT-clones. Hence, ectopically introduced <i>miR-29a</i> into RR-clones notably attenuated the wound-healing rate and cell migration, whereas reduced <i>miR-29a</i> 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 <i>miR-29a</i> significantly eliminated the radioresistance-enhanced lung locomotion. Our data provide evidence suggesting that <i>miR-29a</i> is a promising <i>microRNA</i> 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 (<i>miR-29a</i>) 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.