Resistance to doxorubicin correlated with dysregulation of microRNA-451 and P-glyoprotein, caspase 3, estrogen Receptor on Breast Cancer cell line

Abstract

Doxorubicin (Dox) has been used widely in breast cancer therapy. One of the problems in chemotherapy is the development of resistance to chemotherapy that lead to metastasis and relapse aggressiveness of cancer. MicroRNAs (miRNAs) are small non-coding RNA that regulate protein expression and play role in carcinogenesis, as well as cancer chemotherapy resistance. miR-451 is classified as tumour suppressor miRNA, that binds to messenger RNA (mRNA) of MDR1, and leads disruption of P-glycoprotein (Pgp) expression. The study aimed to investigate the association between miR-451 and Pgp related with Dox resistance mechanism. In silico analysis was conducted to predict the binding affinity between miR-451 and mRNA of MDR1. The MCF-7 cell line was used as wild type model, while MCF-7/Dox was used as a model of resistance. qPCR was conducted to calculate miR-451 expression and immunocytochemistry was used to observe Pgp expression. miRNA was down-regulated in both on MCF-7 and MCF-7/Dox. On the other hand, Pgp expression was detectable in the cytoplasmic and cytoplasmic membrane in MCF-7/Dox. The Pgp expression was higher in the MCF-7/Dox compared to MCF-7. In conlusion, the over expression of Pgp is associated with the resistance to MCF-7/Dox. ABSTRAKDoxorubisin (Dox) adalah salah satu kemoterapi yang telah digunakan secara klinis dalam terapi kanker payudara. Salah satu masalah dalam kemoterapi adalah perkembangan resistensi terhadap kemoterapi yang akan mengarah pada metastasis dan kekambuhan agresivitas kanker. MicroRNAs (miRNAs) merupakan untai RNA kecil yang dapat mengatur ekspresi protein dan berperan dalam karsinogenesis, serta resistensi obat kemoterapi. miR-451 diklasifikasikan sebagai miRNA penekan tumor, yang berikatan dengan messenger RNA (mRNA) MDR1 yang, dan menyebabkan gangguan ekspresi P-glycoprotein (Pgp). Tujuan dari penelitian ini adalah untuk memahami hubungan antara miR-451 dan Pgp terkait dengan mekanisme resistensi Dox. Analisis in silico dilakukan untuk memprediksi afinitas pengikatan antara miR-451 dan mRNA MDR1. Sel line MCF-7 digunakan sebagai wild-type sedangkan MCF-7/Dox, digunakan sebagai model resistensi. Kuantifikasi ekspresi miR-451 diukur menggunakan qPCR dan imunositokimia digunakan untuk mengamati ekspresi Pgp. miRNA-451 ditemukan mengalami penurunan ekspresi baik pada sel MCF-7 dan MCF-7/Dox. Dalam penelitian ini, Pgp ditemukan terekspresi dalam membran sitoplasma dan sitoplasma sel MCF-7/Dox dan MCF-7. Ekspresi PgP ditemukan terekspresi lebih tinggi pada MCF-7/Dox dibandingkan dengan MCF-7 wild-type. Dapat disimpulkan, tingkat ekspresi Pgp ini berkaitan dengan resistensi MCF-7/Dox.

Chitosan nanoparticle-mediated effect of antimiRNA-324-5p on decreasing the ovarian cancer cell proliferation by regulation of GLI1 expression

“… 5 , 6 MiRNA-mRNA binding can lead to the inhibition of expression or even degradation of the messenger RNA (mRNA) before becoming a protein. 7 , 8 MiRNA is commonly found dysregulated in various types of cancers including ovarian cancer. The aberrant miRNA expression correlates with the worsening prognosis of patients, so these RNA molecules are often used as biomarkers of certain cancers.…”