The Impact of MiR-200c in Cervical Cancer Chemoresistance
The Impact of MiR-200c in Cervical Cancer Chemoresistance
Farzaneh Karimi,1,*Kazem Dastjerdi ,2
1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran 2. Department of Medical Biotechnology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
Introduction: Cervical cancer is a common gynecological cancer‐related death among women worldwide. Although chemotherapy is an effective treatment for this cancer, resistance to anti-cancer therapy is still considered a major problem that leads to relapse and mortality. A better understanding of drug resistance mechanisms is essential to promote the efficacy of cancer therapeutic strategies. One of the critical leading causes of chemoresistance is the evasion of apoptosis. Activation of caspases as a pivotal step in the induction of apoptosis has two main pathways including extrinsic pathway controlled by tumor necrosis factor (TNF) receptor family and intrinsic apoptotic pathway regulated by B-cell lymphoma 2 (BCL2) family. Accumulating evidence has indicated that in various cancers chemoresistance might be due to the alteration in microRNAs (miRNAs). Therefore, miRNAs dysregulation might control anti-cancer drug resistance. MiR-200c is one of the important miRNAs involved in cervical cancer and can be a novel candidate target for therapeutic methods.
Methods: Several studies have demonstrated that miR-200c plays a considerable role in different types of cancers. In these studies, usually quantitative reverse transcription polymerase chain reaction (qRT-PCR) and real-time PCR were used for investigating the miRNA expression level between resistant and sensitive cancer cell lines. Moreover, to evaluate the chemoresistance characteristics in cancer cells, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used. Western blot and apoptosis assay were also used to reveal the drug resistance mechanisms of miRNA.
Results: Zhu et al. indicated that miR-200c was downregulated while BCL2 was upregulated in gastric and lung cancer cell lines. On the other hand, overexpression of miR-200c sensitized cells to anti-cancer drugs such as vincristine. Therefore, enforced miR-200c expression can reduce BCL2 protein level and sensitize tumor cells to vincristine by inducing apoptosis.
Conclusion: In this review, we propose that upregulation of miR-200c that can sensitize gastric and lung cancer cells to vincristine can also be investigated in cervical cancer cells and provide valuable miRNA-based therapeutic methods to overcome chemoresistance in this cancer.