miR-656-3p inhibits melanomas in vitro and in vivo by inducing senescence via inhibiting LMNB2.

Background: Ultra-Violet Radiation (UVR) is the most significant exogenous contributor to skin aging. UVB causes the senescence of melanocytes, which results in a permanent arrest in the proliferative process. Senescence is also regarded as a physiological tumor-suppressing mechanism of normal cells. However, the mechanism of the relationship between melanocyte senescence and melanoma was not sufficiently clarified.

Methods: Melanocytes and melanoma cells were irradiated with UVB for the indicated time. The miRNA expression profile of melanocytes were obtained by miRNA sequencing and confirmed by real-time PCR. Cell count kit-8 assays, cell cycle assays were also employed to explore the effect of miR-656-3p and LMNB2 on senescence. Dual-luciferase reporter assays were applied to determine the miRNA targets. Finally, a xenograft model and a photoaging model of mice were conducted to verified the function of miR-656-3p in vivo.

Results: Melanoma cells did not alter into a senescence stage and the expressions of miR-656-3p had no significant changes under the same intensity of UVB radiation. miR-656-3p appeared to be upregulated in melanocytes rather than melanoma cells after UVB radiation. miR-656-3p could promote the photoaging of human primary melanocytes by targeting LMNB2. Finally, overexpression of miR-656-3p significantly induced senescence and inhibited the growth of melanomas in vitro and in vivo.

Conclusion: Our work not only demonstrated the mechanism by which miR-656-3p induced the senescence of melanocytes but also proposed a treatment strategy for melanomas by using miR-656-3p to induce senescence.