Background: High-altitude (HA) attracts people for its beauty and adventure. Interestingly,
however, it affects the normal physiology and health due to the hypobaric hypoxic environment. Normal
individuals acclimatize efficiently, but susceptible individuals encounter HA related disorders.
Among these disorders, high-altitude pulmonary edema (HAPE) results into casualties. During acclimatization,
body makes sequential changes in the expression of genes to counterbalance the hypobaric
hypoxia induced stress. In this context, gene regulatory elements, such as transcription factors, DNA
methylation and microRNAs (miRNAs) become relevant. This review, however, will primarily focus
on miRNAs because of its decisive role in maintaining physiological homeostasis, both under normoxic and hypoxic conditions.
Methods: Availing the literature, an in-silico study was performed to explore the anticipated role of miRNAs in
HAPE pathophysiology. Results: We observed robust target based networking among the miRNAs. miR-16, 20b, 22, 206
and 17/92 were reported to have decreased expression in response to hypoxia and inhibit ion channels and increase pulmonary
arterial pressure leading to vascular dysfunction and loss of cellular integrity. Whereas, miR-23b, 26a and 155 inhibit
TGF signaling and contribute to increased pulmonary pressure, while miR-210 inhibits mitochondrial function. Incidentally,
these physiological func- tions associate with HAPE, favoring possible role of miRNAs. Conclusion: It is concluded
that the expression of individual/groups of miRNAs may change differentially under hypobaric hypoxia to modulate
human physiology; however, this needs to be validated for HAPE pathophysiology.