نقش miR-21 به عنوان یک انکوژن واقعی در سرطان پستان
Abstract
1- Introduction
2- Breast cancer
3- Drug resistance
4- miRNA biogenesis
5- miR-21 in BC
6- Expression of miR-21 in cancer tissues and cells
7- Role of miR-21 as a mediator in drug resistance in BC
8- Upstream pathway of miR-21
9- Potential targets of miR-21
10- Conclusion and future perspectives
References
Abstract
Breast cancer (BC) is the most common cancer among women that is responsible for the most of the cancer-related death in worldwide. Drug resistance is remaining as a significant clinical obstacle to treat BC patients effectively. Therefore, to help overcome this problem, it is necessary to understand the mechanisms of drug resistance. microRNAs classify as highly conserved non-coding RNAs (~22 nucleotides) and interact with mRNAs-coding genes for direct post-transcriptional repression. It has been reported that miR-21 is overexpressed and also acts as oncomiR in many human malignancies by targeting of several tumor suppressor genes–associated with apoptosis, proliferation and metastasis. Specifically, it has been reported that miR-21 is responsible for the drug resistance and its overexpression is related to the development of Multi Drug Resistance (MDR) in breast cancer. In this review, we discussed about the role of miR-21 on the drug resistance of breast cancer.
Introduction
Breast cancer (BC) is responsible for the death of approximately 500,000 women per year in the world. Also, more than one million new case of BC is diagnosed across the world per year. The occurrence of BC accounts for 7-8% of the entire number of malignant tumors. Chemotherapy is known as a principal strategy for cancer treatment; however, its application is limited due to drug resistance. Resistance to chemotherapeutics is mainly divided into two extensive categories: (i) intrinsic and (ii) acquired. Intrinsic resistance shows the presence of resistance-mediating factors in the tumor before starting of treatment process that makes chemotherapy ineffective. Acquired drug resistance, however, will be developed during of the treatment [1,2]. Drug resistance brings serious clinical obstacles to the prosperous treatment of BC patients. To overcome these problems, a well understanding of the drug resistance mechanisms is definitely required. The molecular mechanism of chemotherapeutic resistance in BC cells is completely complicated, and comprises multiple processes, including epigenetic changes, gene mutation, gene amplification and microRNA expression. miRNAs are short non-coding RNAs (~22 nucleotides) that could be found in all eukaryotic cells. They have a significant role in the progression of cancer by binding to the 3' untranslated region (UTR) of the target genes, leading to the target mRNA degradation and inhibition of translation.