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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%–85% of total cases and leading to millions of deaths worldwide. Drug resistance is the primary cause of treatment failure in NSCLC, which urges scientists to develop advanced approaches for NSCLC treatment. Among novel approaches, the miRNA-based method has emerged as a potential approach as it allows researchers to modulate target gene expression. Subsequently, cell behaviors are altered, which leads to the death and the depletion of cancer cells. It has been reported that miRNAs possess the capacity to regulate multiple genes that are involved in various signaling pathways, including the phosphoinositide 3-kinase, receptor tyrosine kinase/rat sarcoma virus/mitogen-activated protein kinase, wingless/integrated, retinoblastoma, p53, transforming growth factor β, and nuclear factor-kappa B pathways. Dysregulation of these signaling pathways in NSCLC results in abnormal cell proliferation, tissue invasion, and drug resistance while inhibiting apoptosis. Thus, understanding the roles of miRNAs in regulating these signaling pathways may enable the development of novel NSCLC treatment therapies. However, a comprehensive review of potential miRNAs in NSCLC treatment has been lacking. Therefore, this review aims to fill the gap by summarizing the up-to-date information on miRNAs regarding their targets, impact on cancer-associated pathways, and prospective outcomes in treating NSCLC. We also discuss current technologies for delivering miRNAs to the target cells, including virus-based, non-viral, and emerging extracellular vesicle-based delivery systems. This knowledge will support future studies to develop an innovative miRNA-based therapy and select a suitable carrier to treat NSCLC effectively.

Malignant pleural mesothelioma (MPM) is an aggressive tumour resistant to treatments. It has been postulated that cancer stem cells (CSCs) persist in tumours causing relapse after multimodality treatment. In the present study, a novel miRNA-based therapy approach is proposed. MPM-derived spheroids have been treated with exosome-delivered miR-126 (exo-miR) and evaluated for their anticancer effect. The exo-miR treatment increased MPM stem-cell like stemness and inhibited cell proliferation. However, at a prolonged time, the up taken miR-126 was released by the cells themselves through exosomes; the inhibition of exosome release by an exosome release inhibitor GW4869 induced miR-126 intracellular accumulation leading to massive cell death and in vivo tumour growth arrest. Autophagy is involved in these processes; miR-126 accumulation induced a protective autophagy and the inhibition of this process by GW4869 generates a metabolic crisis that promotes necroptosis, which was associated with PARP-1 over-expression and cyt-c and AIF release. Here, for the first time, we proposed a therapy against CSCs, a heterogeneous cell population involved in cancer development and relapse.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by low levels of full-length survival motor neuron (SMN) protein due to the loss of the survival motor neuron 1 (SMN1) gene and inefficient splicing of the survival motor neuron 2 (SMN2) gene, which mostly affects alpha motor neurons of the lower spinal cord. Despite the U.S. Food and Drug Administration (FDA) approved SMN-dependent therapies including Nusinersen, Zolgensma® and Evrysdi™, SMA is still a devastating disease as these existing expensive drugs may not be sufficient and thus, remains a need for additional therapies. The involvement of microRNAs (miRNAs) in SMA is expanding because miRNAs are important mediators of gene expression as each miRNA could target a number of genes. Hence, miRNA-based therapy could be utilized in treating this genetic disorder. However, the delivery of miRNAs into the target cells remains an obstacle in SMA, as there is no effective delivery system to date. This review highlights the potential strategies for intracellular miRNA delivery into target cells and current challenges in miRNA delivery. Furthermore, we provide the future prospects of miRNA-based therapeutic strategies in SMA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are non-coding RNAs generated from endogenous hairpin-shaped transcripts that powerfully regulate gene expression at post-transcriptional level. Each miRNA is capable to regulate the expression levels of hundreds of transcripts and each mRNA may have more than one miRNA recognition sequence. There is emerging evidence that deregulation of miRNA expression leads to the alteration of pivotal physiological functions contributing to the development of diseases and neoplasms, including pituitary adenoma. This review is aimed at providing the up-to-date knowledge concerning deregulated miRNAs of pituitary tumors and their functions. In order to take stock, pituitary tumors have been sub-divided in different classes on the basis of tumor features (histotype, dimension, aggressiveness). The overview takes full consideration of the recent advances in miRNAs role as potential therapeutics and biomarkers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)