Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models

Murdaca, Giuseppe; Tonacci, Alessandro; Negrini, Simone; Greco, Monica; Borro, Matteo; Puppo, Francesco; Gangemi, Sebastiano

s of antagomiRs was demonstrated in humans, as well as in animals and cell lines without particular differences between those three aggregated groups. According to our results, the miRNA most frequently retrieved in lung conditions, therefore considered as "organ-specific," although not "disease-specific," appears to be miR-21, which has been found to be somewhat involved in lung conditions according to six of the selected papers [8, [24] [25] [26] [27] [28] . However, miR-155 was also largely investigated and found to be involved in five works retrieved [29] [30] [31] [32] 72] . Further miRNAs frequently involved in lung conditions include miR-7 and miR-34, included in four articles, and miR-92 and miR-374, with three hits each. As evidenced, despite a handful miRNAs with multiple hits across the works included in our research, the only critical issue eventually identified for our approach concerns the right choice for the miRNA to be downregulated to achieve the expected result of the whole As shown in Tables 1-5, the vast majority of them included research carried out on cell lines and on animals, whereas only a few (20, corresponding to 29.4%) investigated the selected topic on humans. As expected, the condition most widely investigated was lung cancer (21/68), followed by pulmonary hypertension (7/68). All of the selected papers took into account the efficacy of the antagomiR treatment on the various diseases, whereas safety was rarely investigated (only in two cases out of 68). Overall, the use of antagomiR was seen to be efficient in downregulating the specific miRNA they are conceived for, with quite similar results either in vivo and in vitro and independently from the disease and the cell line they are used for. Overall, the usefulness of antagomiRs was demonstrated in humans, as well as in animals and cell lines without particular differences between those three aggregated groups. According to our results, the miRNA most frequently retrieved in lung conditions, therefore considered as "organ-specific," although not "disease-specific," appears to be miR-21, which has been found to be somewhat involved in lung conditions according to six of the selected papers [8, [24] [25] [26] [27] [28] . However, miR-155 was also largely investigated and found to be involved in five works retrieved [29] [30] [31] [32] 72] . Further miRNAs frequently involved in lung conditions include miR-7 and miR-34, included in four articles, and miR-92 and miR-374, with three hits each. As evidenced, despite a handful miRNAs with multiple hits across the works included in our research, the only critical issue eventually identified for our approach concerns the right choice for the miRNA to be downregulated to achieve the expected result of the whole process. Indeed, even taking into account a single disease (e.g., lung cancer) on a similar population (e.g., on humans), a plethora of miRNAs with different functions can be identified as associated with the pathological process, therefore the selection of the right process to be blocked or, conversely, enhanced, is critical for good outcome of the process. Taking into account some specific disease categories, the first one to be analyzed, due to its numerical prevalence, was lung cancer. Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1, and suppresses markers of cellular senescence, restoring cellular growth (p < 0.05) Inhibition of elevated miR