Peran Hsa-miR-4454 pada penuaan kulit: Studi klinis dan bioinformatik
DOI:
https://doi.org/10.25170/djm.v24i1.5627Keywords:
ATM, MAPK14, mikroRNA, miR-4454, penuaan kulitAbstract
Pendahuluan: Penuaan kulit adalah proses kompleks yang melibatkan faktor intrinsik dan ekstrinsik. Berbagai parameter untuk mengevaluasi karakteristik kulit telah diusulkan. Namun, biomarker yang akurat untuk penuaan kulit dan hubungan mekanisme molekuler penuaan kulit masih sangat terbatas. Penelitian ini bertujuan untuk memvalidasi peran mikroRNA (miRNA) dalam regulasi epigenetik penuaan kulit sebagai kandidat biomarker dan target terapi.
Metode: Profil ekspresi miRNA kakek dan cucu dari 2 famili Jawa dibandingkan untuk memilih kandidat miRNA yang memiliki perbedaan ekspresi pada jaringan kulit. Selanjutnya, miRNA yang mengalami perubahan ekspresi tersebut dianalisis fungsi dan perannya pada tingkat molekuler dengan pendekatan bioinformatika.
Hasil: Hasil profiling menunjukkan miR-4454 yang konsisten mengalami peningkatan ekspresi pada kedua famili yaitu sebesar 3,318 pada famili I dan 9,315 pada famili II. Berdasarkan data dari GeneCards, miR-4454 memiliki ekspresi yang cukup tinggi pada kulit dan diekspresikan pada seluruh komponen sel. Analisis data dari GWAS mengindikasikan bahwa miR-4454 terlibat dalam pengaturan panjang telomer. Analisis gen target dengan menggunakan TargetScanHuman, miRTarBase, miRTargetLink dilanjutkan dengan pengayaan ontologi gen dan jalur molekuler dengan platform EnrichR menunjukkan miR-4454 berperan dalam regulasi produksi IL-12, respons terhadap radiasi, autofagi, metabolisme, FoxO signaling pathway, dan cellular senescence. Gen ataxia telangiectasia mutated (ATM) dan mitogen-activated protein kinase 14 (MAPK14) diduga berperan penting pada regulasi penuaan kulit akibat miR-4454 karena keterlibatannya pada cellular senescence.
Simpulan: Pada penuaan kulit, ekspresi miR-4454 yang tinggi berpotensi digunakan sebagai kandidat biomarker dan dasar pengembangan target terapi. Gen ATM dan MAPK14 merupakan dua kandidat target miR-4454.
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