The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.

Glycolysis in human cancers: Emphasis circRNA/glycolysis axis and nanoparticles in glycolysis regulation in cancer therapy.

The metabolism of cancer has been an interesting hallmark and metabolic reprogramming, especially the change from oxidative phosphorylation in mitochondria to glucose metabolism known as glycolysis occurs in cancer. The molecular profile of glycolysis, related molecular pathways and enzymes involved in this mechanism such as hexokinase have been fully understood. The glycolysis inhibition can significantly decrease tumorigenesis. On the other hand, circRNAs are new emerging non-coding RNA (ncRNA) molecules with potential biological functions and aberrant expression in cancer cells which have received high attention in recent years. CircRNAs have a unique covalently closed loop structure which makes them highly stable and reliable biomarkers in cancer. CircRNAs are regulators of molecular mechanisms including glycolysis. The enzymes involved in the glycolysis mechanism such as hexokinase are regulated by circRNAs to modulate tumor progression. Induction of glycolysis by circRNAs can significantly increase proliferation rate of cancer cells given access to energy and enhance metastasis. CircRNAs regulating glycolysis can influence drug resistance in cancers because of theirimpact on malignancy of tumor cells upon glycolysis induction. TRIM44, CDCA3, SKA2 and ROCK1 are among the downstream targets of circRNAs in regulating glycolysis in cancer. Additionally, microRNAs are key regulators of glycolysis mechanism in cancer cells and can affect related molecular pathways and enzymes. CircRNAs sponge miRNAs to regulate glycolysis as a main upstream mediator. Moreover, nanoparticles have been emerged as new tools in tumorigenesis suppression and in addition to drug and gene delivery, then mediate cancer immunotherapy and can be used for vaccine development. The nanoparticles can delivery circRNAs in cancer therapy and they are promising candidates in regulation of glycolysis, its suppression and inhibition of related pathways such as HIF-1α. The stimuli-responsive nanoparticles and ligand-functionalized ones have been developed for selective targeting of glycolysis and cancer cells, and mediating carcinogenesis inhibition.

Functions and therapeutic interventions of non-coding RNAs associated with TLR signaling pathway in atherosclerosis.

Nowadays, emerging data demonstrate that the toll-like receptor (TLR) signaling pathway plays an important role in the progression of inflammatory atherosclerosis. Indeed, dysregulated TLR signaling pathway could be a cornerstone of inflammation and atherosclerosis, which contributes to the development of cardiovascular diseases. It is interesting to note that this pathway is heavily controlled by several mechanisms, such as epigenetic factors in which the role of non-coding RNAs (ncRNAs), particularly microRNAs and long noncoding RNAs as well as circular RNAs in the pathogenesis of atherosclerosis has been well studied. Recent years have seen a significant surge in the amount of research exploring the interplay between ncRNAs and TLR signaling pathway downstream targets in the development of atherosclerosis; however, there is still considerable room for improvement in this field. The current study was designed to review underlying mechanisms of TLR signaling pathway and ncRNA interactions to shed light on therapeutic implications in patients with atherosclerosis.

Mitofusin-2 in cancer: Friend or foe?

Cancer is a category of disorders characterized by excessive cell proliferation with the ability to infiltrate or disseminate to other organs of the body. Mitochondrial dysfunction, as one of the most prominent hallmarks of cancer cells, has been related to the onset and development of various cancers. Mitofusin 2 (MFN2) is a major mediator of mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria interaction, mitophagy and axonal transport of mitochondria. Available data have shown that MFN2, which its alterations have been associated with mitochondrial dysfunction, could affect cancer initiation and progression. In fact, it showed that MFN2 may have a double-edged sword effect on cancer fate. Precisely, it demonstrated that MFN2, as a tumor suppressor, induces cancer cell apoptosis and inhibits cell proliferation via Ca2+ and Bax-mediated apoptosis and increases P21 and p27 levels, respectively. It also could suppress cell survival via inhibiting PI3K/Akt, Ras-ERK1/2-cyclin D1 and mTORC2/Akt signaling pathways. On the other hand, MFN2, as an oncogene, could increase cancer invasion via snail-mediated epithelial-mesenchymal transition (EMT) and in vivo tumorigenesis. While remarkable progress has been achieved in recent decades, further exploration is required to elucidate whether MFN2 could be a friend or it's an enemy. This study aimed to highlight the different functions of MFN2 in various cancers.