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.

Adsorption of Thiotepa anticancer drugs on the BC3 nanotube as a promising nanocarriers for drug delivery.

By applying periodic DFT computations, the possible employment of BC3 nanotube (BC3NT) as a drug delivery system (DDS) for Thiotepa (TPA) anticancer medicine has been examined. Quantum mechanics computations by the B3LYP-6-31 +G(d,p) method with dispersion correction including to be used for calculation the details of electronic, geometric, and energetic features of the interactions between TPA drug and BC3NT. The appropriate orientation for the TPA interacting with BC3NT has been assessed and adsorption energies (ΔEad) have been computed. The band distance of S and B atom in complex C2 is about 1.89 Å, also the value of ΔEad of - 29.83 kcal/mol in most stable compounds. By applying frontier molecular orbital analysis, it has been assessed that during stimulation, TPA medicine performs as HOMO and delivers the charge towards the LUMO, i.e., BC3NT. In the aqueous phase, the λmax of BC3NT-AP complex is blue-shifted by 36 nm. Drug delivery to the specific cells after protonation has been studied, due to the point that cancer cells have lower pH than others. The value of computed solvation energy (ΔEsolvation) shows the solubility BC3NT@TPA system in the water phase. The effects of the present investigation verified the ability of BC3NT as a drug delivery agent for TPA in the treatment of cancer.