MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19

Table 1 Direct gene targets of microRNA-155 relevant to renin-angiotensin system and immune system in severe acute respiratory coronavirus-2 infection

Gene symbol	Full gene name	Action
AGTR1	Angiotensin II type 1 receptor gene	AGTR1 gene repression downregulates its translation, thereby lowering AT1R membrane expression and downstream signalling, like endogenous AT1R blockade redirecting Ang II towards its alternative receptor Ang II type 2 receptor
ARG2	Arginase2	Repressed translation allows increased L-arginine availability to generate nitric oxide supporting immune cell function and beneficially regulating inflammatory responses in the lung
BACH1	BTB and CNC homology 1, basic leucine zipper transcription factor 1	Translational repression of BACH1 leads to potent anti-inflammatory, cytoprotective, antioxidant programs through heme oxygenase-1
Ets-1	E26 transformation-specific sequence-1	Ets-1 translational repression prevents Ang II/AT1R-mediated gene upregulation involved in inflammation, fibrosis, vascular remodeling, and cardiac hypertrophy
CACNA1C(Cav1.2)	L-type calcium channel	CACNA1C forms part of the LTCC that mediates reactive oxygen species production and calcium influx in vascular smooth muscle cells, causing vasoconstriction and oxidative stress, both important components of vascular aging. These attributes are contained by miR-155-induced translational repression
SOCS1	Suppressor of cytokine signaling 1	SOCS1 negatively regulates type I IFN signaling, thus, its translational repression enhances type I IFN-mediated antiviral response. Erythropoietin’s protective effects in ischemic injury are mediated through the Janus kinase 2/Y343/signal transducers and activators of transcription 5 pathway, enhanced via miR-155-induced SOCS1 repression

AGTR1: Angiotensin II type 1 receptor gene; Ang: Angiotensin; ARG2: Arginase 2 gene; AT1R: Angiotensin II type 1 receptor; BACH1: BTB and CNC homology 1, basic leucine zipper transcription factor 1 gene; Ets-1: E26 transformation-specific sequence-1 gene; IFN: Interferon; LTCC: L-type calcium channel; MiR-155: MicroRNA-155; SOCS1: Suppressor of cytokine signaling 1 gene.