MicroRNAs: master regulators of drug resistance, stemness, and metastasis

Abstract

MicroRNAs (miRNAs) are 20-22 nucleotides long small non-coding RNAs that regulate gene expression post-transcriptionally. Last decade has witnessed emerging evidences of active roles of miRNAs in tumor development, progression, metastasis, and drug resistance. Many factors contribute to their dysregulation in cancer, such as chromosomal aberrations, differential methylation of their own or host genes' promoters and alterations in miRNA biogenesis pathways. miRNAs have been shown to act as tumor suppressors or oncogenes depending on the targets they regulate and the tissue where they are expressed. Because miRNAs can regulate dozens of genes simultaneously and they can function as tumor suppressors or oncogenes, they have been proposed as promising targets for cancer therapy. In this review, we focus on the role of miRNAs in driving drug resistance and metastasis which are associated with stem cell properties of cancer cells. Furthermore, we discuss systems biology approaches to combine experimental and computational methods to study effects of miRNAs on gene or protein networks regulating these processes. Finally, we describe methods to target oncogenic or replace tumor suppressor miRNAs and current delivery strategies to sensitize refractory cells and to prevent metastasis. A holistic understanding of miRNAs' functions in drug resistance and metastasis, which are major causes of cancer-related deaths, and the development of novel strategies to target them efficiently will pave the way towards better translation of miRNAs into clinics and management of cancer therapy.

Low expression of miR-1469 predicts disease progression and unfavorable post-surgical clinical outcomes in patients with esophageal squamous cell cancer

“…m iR NAs a re deregulated in numerous human cancers (23,24). Previous studies have demonstrated that miRNAs are reliable and cost-effective biomarkers that can be utilized in the diagnosis and assessment of the progression, therapeutic response and prognosis of a wide spectrum of malignant tumors, including esophageal cancer (7,(25)(26)(27). A better understanding of the miRNAs associated with particular cancers would provide valuable insights for treatment.…”

miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance

“…In addition, involvement of miRNAs in combined regulation of drug resistance and EMT is evident [74]. Likewise, miR-200c, a negative regulator of EMT, has shown great potential to overcome both chemotherapy and targeted therapy resistance through reversing the EMT process or promoting epithelial-like state (Fig.…”

MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

“…MiRNAs regulate a wide array of cell functions such as proliferation, differentiation, migration, and apoptosis, and are implicated in various pathological conditions including tumorigenesis [4-7]. Accumulating evidence also suggests that dysregulation of specific miRNAs may be involved in the acquisition of drug resistance of a number of cancers, particularly lung cancer [8, 9]. Identifying miRNAs implicated in NSCLC and understanding the mechanisms by which they regulate NSCLC tumorigenesis and/or drug resistance is of critical importance in seeking to improve NSCLC treatment.…”