Skip to main content

ORIGINAL RESEARCH article

Front. Med.
Sec. Dermatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1485224
This article is part of the Research Topic Advances and Novel Intervention in Photodermatology View all 3 articles

MiR-4298 and lncKRTAP5-6-3 regulated Cathepsin D expression through ERK-MAPK signaling pathway in chronic UVB-damaged HaCaT cells

Provisionally accepted
Xinling Chen Xinling Chen 1Feng Zhou Feng Zhou 1Yao Lin Yao Lin 2*Jie Zhang Jie Zhang 1Yue Xia Yue Xia 1*Wenyi Hou Wenyi Hou 1*Yu Sun Yu Sun 3*Wei Lai Wei Lai 1*Yue Zheng Yue Zheng 3*
  • 1 Department of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • 2 Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guang Zhou, China
  • 3 Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Objective: MiRNAs and lncRNAs were important regulators in skin photoaging process. In this study, we investigated the expression changes and interactions between miR4298 and lncKRTAP5-6-3 in chronically UVB damaged human keratinocyte cell line (HaCaT) cells, and explored miR4298-MAPK/ERK signaling pathway-Cathepsin D-lncKRTAP5-6-3 mechanisms in photoaging cells.Methods: HaCaT cells were irradiated with 12 mJ/cm 2 UVB once a day for 7 days. miR-4298 mimics and miR-4298 inhibitors were transfected into HaCaT cells by lipo3000 transfection reagent, and the HaCaT cells were divided into three groups: ①blank control group; ②UVB damaged group; and ③ UVB damage+miR-4298 regulation (overexpression or inhibition) group. The changes of miR4298 and lncKRTAP5-6-3 expression were quantitatively analyzed using RT-PCR, and the expression of Cathepsin D and MAPK/ERK signaling pathway proteins were detected by Western blot.Results: After 7 consecutive days of UVB irradiation, the expression of miR-4298 decreased by 0.64 ± 0.06 (P＜0.001) compared to the un-irradiated HaCaT cells, and the expression of the KRTAP5-6-3 decreased by 0.80 ± 0.13 (P＜0.001) compared to the control group. The expression of p-ERK signaling was increased by 0.9437 ± 0.1186 (P < 0.0001) and Cathepsin D was decreased by 0.6163 ± 0.075 (P<0.0001). In HaCaT cells transfected with miR-4298 mimics and then irradiated by UVB for 7 days, the expression of lncKRTAP5-6-3 was increased to 0.5114 ± 0.1438 (P＜0.05) folds, and the phosphorylation level of ERK signaling was decreased by 0.3880 ± 0.1185 (P < 0.01), while Cathepsin D expression was increased 0.2617 ± 0.0749 (P<0.0001) compared to the UVB damaged group. In HaCaT cells transfected with miR-4298 inhibitors and then irradiated by UVB for 7 days, lncKRTAP5-6-3 was decreased by 0.1697 ± 0.1383, the phosphorylation level of ERK signaling was increased 1.096 ± 0.7836 (P < 0.05), while Cathepsin D expression was decreased by 0.05197 ± 0.24827 compared to the UVB damaged group. Conclusion: Synergistic effects of miR4298 and lncKRTAP5-6-3 play important roles in chronic UVB-damaged HaCaT cells by regulating MAPK/ERK signaling pathway and Cathepsin D expression. This study presents novel targets for intervening for chronic ultraviolet damage (photoaging) skin and UV-related dermatoses.

    Keywords: Chronic UV damage, miR4298, lncRNA, ERK-MAPK signaling pathway, Cathepsin D

    Received: 23 Aug 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Chen, Zhou, Lin, Zhang, Xia, Hou, Sun, Lai and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yao Lin, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guang Zhou, China
    Yue Xia, Department of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Wenyi Hou, Department of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Yu Sun, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China
    Wei Lai, Department of Dermato-Venereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    Yue Zheng, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.