Cancer remains one of the leading causes of death worldwide, with an estimated 2 million new diagnoses and over 600,000 deaths in the United States in 2025 alone, but there is still no cure for the disease. Recent developments have suggested the potential of the microRNA (miRNA) miR-615 as novel therapeutic target in cancer. Specifically, the association of the intronic miR-615 with poor prognosis has been observed in various types of cancer, such as esophageal, renal, and lung cancers. The overexpression of miR-615-3p and HOXC5 is believed to increase the viability, proliferation, and migration of these cancer cells by inhibiting hTERT protein expression, which is the protein component of the telomerase enzyme. We noted that the sequence of pre-miR-615 is G-rich and hypothesized that it could form a G-quadruplex structure which could impact the mature levels of this miRNA. The GQ structure formation was demonstrated by biophysical methods, such as 1H nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD) spectroscopy, native polyacrylamide gel electrophoresis, and UV thermal denaturation spectroscopy. Thus, this study identifies a potential novel therapeutic target in cancer as stabilizing/destabilizing this pre-miR-615 GQ structure will lead to the alteration of the mature miR-615-3p levels.
Garza et al. (Sun,) studied this question.