Artikel Review: Interaksi Silang Pensinyalan WNT dan TGF-β pada  Kanker Paru dengan MikroRNA sebagai Mayoritas Regulator

Nita Rahmasari; Melisa I. Barliana; Riezki Amalia

doi:10.15416/ijcp.2021.10.1.62

Artikel Review: Interaksi Silang Pensinyalan WNT dan TGF-β pada Kanker Paru dengan MikroRNA sebagai Mayoritas Regulator

Nita Rahmasari, Melisa I. Barliana, Riezki Amalia

Abstract

Posisi pertama untuk kejadian dan mortalitas kanker paru di dunia saat ini masih menjadi tantangan untuk menemukan dan mengembangkan terapi potensial bagi pasien kanker paru. Pemahaman pada tingkat molekular mengenai progres tumor pada kanker sangat diperlukan untuk menemukan rejimen terapi yang efektif; terdapat perubahan genetik pada berbagai jalur pensinyalan pengatur proses biologi yang terlibat selama karsinogenesis. Pensinyalan WNT dan TGF-β telah banyak diidentifikasi pada beberapa penelitian, khususnya mengenai interaksi keduanya dalam tumorigenesis paru, namun belum cukup diulas secara jelas. Oleh karena itu, dilakukan pengkajian terhadap 10 artikel riset yang diakses secara online melalui database MeSH PubMed dengan kata kunci “Receptors, Wnt/Wnt Signaling Pathway/Wnt Proteins” AND “Receptors, Transforming Growth Factor beta/Transforming Growth Factor beta” AND “Lung Neoplasms/Small Cell Lung Carcinoma/Carcinoma, Non-Small-Cell Lung”, untuk menyusun ulasan mengenai interaksi silang keduanya pada kanker paru secara lebih jelas. Secara menyeluruh, interaksi silang antara pensinyalan WNT dan TGF-β meregulasi pemrograman Cancer Stem Cell (CSC) dan Epithelial–Mesenchymal Transition (EMT) selama tumorigenesis dan prognosis kanker paru yang berdampak pada metastasis, peningkatan agresivitas, serta kemoresistensi tumor. Interaksi silang pensinyalan WNT dan TGF-β pada kanker paru dapat terjadi secara langsung pada tingkat kompleks transkripsi mereka ataupun dengan melibatkan suatu mediator penting, yang sebagian besarnya diperankan oleh mikroRNA. Terdapat berberapa mikroRNA yang telah teridentifikasi baik pada kanker paru dalam meregulasi interaksi silang antara pensinyalan WNT dan TGF-β, seperti miR-1827, miR-3127-5p, dan miR-128-3p. Pembahasan ini mengimplikasikan peluang yang tinggi pada penekanan kedua jalur WNT dan TGF-β secara simultan dan efektif dengan menargetkan suatu molekul yang berpotensi untuk kanker paru.

Kata kunci: Interaksi silang pensinyalan, kanker paru, pensinyalan TGF-β, pensinyalan WNT

Review Article: Crosstalk between WNT and TGF-β signaling in Lung Cancer with MicroRNA as Majority of Regulators

Abstract

The discovery and development of potential therapies to reduce the incidence and mortality of lung cancer is still a challenge. Consequently, identifying an effective therapeutic regimen is necessary for tumor progression in cancer at the molecular level due to genetic changes in various signaling pathways that regulate the biological processes involved during carcinogenesis. WNT and TGF-β signaling have been widely identified in several studies, with regards to the interaction of both in pulmonary tumorigenesis although they have not been adequately reviewed clearly. Hence, an assessment of 10 research articles was conducted online through the MeSH PubMed database with the keywords “Receptors, Wnt/Wnt Signaling Pathway/Wnt Proteins” AND “Receptors, Transforming Growth Factor beta/Transforming Growth Factor beta” AND “Lung Neoplasms/Small Cell Lung Carcinoma/Carcinoma, Non-Small-Cell Lung”, to compile an overview of the crosstalk. Furthermore, the crosstalk between WNT and TGF-β signaling regulates the programming of Cancer Stem Cell (CSC) and Epithelial–Mesenchymal Transition (EMT) during tumorigenesis and prognosis of lung cancer that leads to metastasis, increased aggressiveness, and tumor chemoresistance. The crosstalk of WNT and TGF-β signaling in lung cancer can occur directly at the level of their transcription complex or by involving an important mediator, most of which is played by microRNA. There are several microRNAs identified in regulating crosstalk between WNT signaling and TGF-β, such as miR-1827, miR-3127-5p, and miR-128-3p. The discussion implies a high opportunity for the simultaneous and effective suppression of both WNT and TGF-β pathways by targeting a molecule that has the potential for lung cancer.

Keywords: Lung cancer, signaling crosstalk, TGF-β signaling, WNT signaling

Keywords

Interaksi silang pensinyalan, kanker paru, pensinyalan TGF-β, pensinyalan WNT

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