Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT)

Abstract

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression.

Figure 1

Representative signaling pathways of apoptosis induced by photodynamic therapy (PDT). Depending on the nature of the photosensitizer and its intracellular localization, the initial photodamage can involve different molecules, with the consequent activation of specific death pathways that converge on mitochondria. Mitochondria-localized photosensitizer can cause immediate and light-dependent photodamage to the anti-apoptotic Bcl-2 and Bcl-xL proteins, prompting the release of caspase-activating molecules. Lysosomal hydrolases and ER stress also induce Bax-mediated caspase activation.

Figure 2

Expression of miR-210 and miR-296 after PDT in HeLa cells. miR-210 and miR-296 expression levels were significantly increased 1 h after PDT (60 mW/cm², 90 s) in cells treated with 50 μg/mL talaporfin sodium relative to levels in the control group (i.e., talaporfin sodium concentration of 0 μg/mL) (1 × 10⁴ cells/well). The asterisk, * indicates p < 0.05, a significant difference between the relative expression levels of PDT-treated cells and non-PDT-treated cells. All experiments were performed four times independently. All data are expressed as the means ± SD of four replicates from four experiments (Adapted from [120]).