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
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...
Saved in:
| Published in: | SLAS discovery Vol. 27; no. 4; pp. 258 - 265 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
01-06-2022
Elsevier |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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.
This study strived to evaluate the effect of miR-K12–1 on the progression of HIV-related gastrointestinal KS.
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.
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.
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. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 2472-5552 2472-5560 |
| DOI: | 10.1016/j.slasd.2022.04.001 |