SLAS Discovery (Jun 2022)
Kaposi's sarcoma-associated herpes virus-derived microRNA K12–1 over-activates the PI3K/Akt pathway to facilitate cancer progression in HIV-related gastrointestinal Kaposi's sarcoma
Abstract
Background: Kaposi's sarcoma-associated herpes virus (KSHV) initiate and accelerate the development of Kaposi's sarcoma (KS), and KSHV possesses many cancer-associated genes, including KSHV-derived microRNA miR-K12–1, which has been identified to be closely associated with KS progression. However, the detailed mechanisms by which miR-K12–1 facilitates HIV-related gastrointestinal KS development are still not fully delineated. Objectives: This study strived to evaluate the effect of miR-K12–1 on the progression of HIV-related gastrointestinal KS. Materials and methods: The expression levels of miR‐K12–1 in HIV-related gastrointestinal KS tissues were determined by RT‐qPCR. Proliferation and apoptosis were assessed by colony formation, CCK-8 and flow cytometry, respectively. The expression of all proteins was detected by Western blot. The in vivo effect of miR‐K12–1 on the formation of a tumor was explored by using the mouse xenograft model. Results: In this study, we uncovered that KSHV-miR-K12–1 was upregulated in HIV-related gastrointestinal KS tissues and associated with poor outcome in HIV-related gastrointestinal KS patients. Compared with the control group, after miR-K12–1 inhibitor transfection, BCBL-1 cell viability was decreased, and the cell apoptosis was significantly increased, whereas transfection of miR-K12–1 mimics promoted cell proliferation and mitosis. In addition, our rescuing experiments verified that miR-K12–1 promoted cell proliferation via activating the PI3K/Akt pathway, and inhibition of the PI3K/Akt pathway by LY294002 abrogated the tumor-promoting effects of miR-K12–1 in HIV-related gastrointestinal KS. Conclusions: In summary, we concluded that KSHV-derived miR-K12–1 activate the PI3K/Akt pathway to initiate and accelerate the development of KS, which convinces us that miR-K12–1 can be used as potential biomarkers for KS diagnosis, treatment and prognosis.
