Latar Belakang : Melanoma merupakan kanker kulit yang berasal dari melanosit, sel turunan krista neural, dan memiliki tingkat mortalitas tinggi akibat kemampuan metastasis yang agresif. Berbeda dengan kanker epitel, melanoma tidak mengalami EMT klasik, melainkan proses yang dikenal sebagai phenotype switching, yaitu perubahan dinamis antara fenotipe proliferatif dan fenotipe invasif. Perubahan ini ditandai dengan peningkatan ekspresi N-cadherin (CDH2) yang berkontribusi terhadap peningkatan migrasi, invasi, dan kemampuan metastasis sel tumor. Regulasi perubahan fenotipe ini diduga melibatkan mekanisme epigenetik, termasuk miRNA, yang berperan dalam mengatur ekspresi gen-gen kunci pada jalur pertumbuhan dan progresi tumor.
Tujuan : Penelitian ini bertujuan untuk menganalisis hubungan antara kelompok miRNA yang secara dominan mengatur ekspresi CDH2 pada proses EMT di Melanoma.
Metode : Studi observasional analitik dengan desain potong lintang dan pendekatan retrospektif menggunakan data sekunder dari TCGA-SKCM (368 sampel tumor primer dan metastasis melanoma kulit). Sampel dikelompokkan berdasarkan ekspresi CDH2 tinggi dan rendah. Analisis miRNA diekspresikan berbeda (FDR < 0>miRNA teratas untuk dianalisis lebih lanjut. Interaksi miRNA–mRNA dilakukan menggunakan miRNet dan analisis jalur biologis menggunakan DAVID.
Hasil : Ditemukan perbedaan profil miRNA antara kelompok CDH2 tinggi dan rendah pada melanoma primer dan metastasis. Pada primer, 10 miRNA meningkat pada CDH2 tinggi. Pada metastasis, 22 miRNA meningkat dan 3 miRNA menurun pada CDH2 tinggi. Gen target terutama terlibat dalam jalur MAPK, PI3K–Akt, regulasi siklus sel, dan p53 signaling.
Kesimpulan : Penelitian ini menunjukkan perbedaan regulasi miRNA pada melanoma dengan ekspresi CDH2 tinggi antara fase primer dan metastasis. Pada fase primer, miRNA seperti hsa-miR-21-5p, hsa-miR-9-3p, dan hsa-miR-206 memodulasi jalur MAPK dan PI3K–Akt. Pada metastasis, peningkatan hsa-miR-125b-5p, hsa-miR-214- 5p, dan hsa-miR-149-3p berkaitan dengan penekanan gen tumor suppressor, sedangkan penurunan hsa-miR-203a-3p dan hsa-miR-211-5p menyebabkan aktivasi siklus sel. Validasi eksperimental dan integrasi data klinis diperlukan untuk memperkuat temuan.
Background: Melanoma is a malignant skin cancer derived from melanocytes, neural crest–origin cells, and is associated with high mortality due to its aggressive metastatic potential. Unlike epithelial cancers, melanoma does not undergo classical epithelial– mesenchymal transition (EMT) but instead exhibits a process known as phenotype switching, characterized by dynamic transitions between proliferative and invasive states. This transition is marked by increased N-cadherin (CDH2) expression, which contributes to enhanced migration, invasion, and metastatic capacity. Epigenetic mechanisms, including (miRNAs), are believed to regulate this phenotypic shift by modulating key genes involved in tumor growth and progression.
Objective: This study aimed to analyze the association between miRNA expression profiles and CDH2 expression levels in the context of EMT-related processes in melanoma.
Methods: An analytical observational study with a cross-sectional and retrospective design was conducted using secondary data from TCGA-SKCM (368 primary and metastatic cutaneous melanoma samples). Samples were stratified based on high and low CDH2 expression. Differentially expressed miRNAs were identified using an FDR cutoff < 0>
Results: Distinct miRNA expression profiles were observed between CDH2-high and CDH2-low groups in both primary and metastatic melanoma. In primary tumors, 10 miRNAs were upregulated in the CDH2-high group. In metastatic tumors, 22 miRNAs were upregulated and 3 were downregulated in the CDH2-high group. Target genes were predominantly involved in the MAPK pathway, PI3K–Akt pathway, cell cycle regulation, and p53 signaling.
Conclusion: This study demonstrates differential miRNA regulation in CDH2-high melanoma between primary and metastatic stages. In primary melanoma, miRNAs such as hsa-miR-21-5p, hsa-miR-9-3p, and hsa-miR-206 modulate MAPK and PI3K– Akt signaling. In metastatic melanoma, upregulated miRNAs including hsa-miR-125b- 5p, hsa-miR-214-5p, and hsa-miR-149-3p are associated with tumor suppressor gene repression, while downregulated miRNAs such as hsa-miR-203a-3p and hsa-miR-211- 5p contribute to cell cycle activation. Experimental validation and integration with clinical data are warranted to strengthen these findings.
Kata Kunci : Melanoma, EMT, CDH2, microRNA
