Effects of the circ_101238/miR‑138‑5p/CDK6 axis on proliferation and apoptosis keloid fibroblasts
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- Published online on: June 19, 2020 https://doi.org/10.3892/etm.2020.8917
- Pages: 1995-2002
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Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
The formation of keloid scars is normally induced by cutaneous injuries, however, the detailed mechanisms underlying keloid formation remain largely unknown. The present study aimed to investigate the effects of circular RNA_101238 (circ_101238) on the proliferation and apoptosis of keloid fibroblasts and to identify the underlying molecular mechanisms of these effects. Reverse transcription‑quantitative (RT‑q)PCR was performed to determine the expression levels of circ_101238, microRNA (miRNA/miR)‑138‑5p and cyclin‑dependent kinase 6 (CDK6) in keloids and normal skin tissues. Following transfection with short hairpin (sh)‑circ_101238, LV‑circ_101238, miR‑138‑5p mimics, miR‑138‑5p inhibitors and small interfering (si)‑CDK6, cell proliferation was assessed using a cell counting kit‑8 assay. Furthermore, cell apoptosis was evaluated via flow cytometric analysis, while a dual‑luciferase assay was performed to confirm interactions between circ_101238, miR‑138‑5p and CDK6. The expression levels of the proliferation marker, CDK6 and apoptosis marker, caspase‑3 were determined via RT‑qPCR and western blot analyses. The results demonstrated that expression levels of circ_101238 and CDK6 were significantly increased in keloid samples, while miR‑138‑5p expression was reduced in comparison to normal skin. Furthermore, circ_101238 was demonstrated to bind miR‑138‑5p, which subsequently targeted CDK6. Proliferative activity and CDK6 expression were significantly decreased in keloid fibroblasts following transfection with sh‑circ_101238 or miR‑138‑5p mimics, while cell apoptosis was markedly increased. Furthermore, co‑transfection with miR‑138‑5p mimics reversed the effects caused by overexpression of circ_101238. Treatment of keloid fibroblasts with si‑CDK6 counteracted the biological behavior changes induced by miR‑138‑5p inhibitors. Additionally, transfection with LV‑CDK6 reversed the effects caused by miR‑138‑5p mimics. Taken together, the results of the present study demonstrated that circ_101238 was upregulated in keloid tissues in comparison with normal tissues and that circ_101238 knockdown inhibited cell proliferation, while promoting apoptosis of keloid fibroblasts via the miR‑138‑5p/CDK6 axis. These results suggest that circ_101238 may serve as a promising therapeutic candidate for keloid therapy and that circ_101238/miR‑138‑5p/CDK6 signaling has the potential to regulate the growth of keloid fibroblasts.
