Journal
CANCER CELL INTERNATIONAL
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12935-020-01481-8
Keywords
Prostate cancer; KCNQ1OT1; MiR-15a; PD-L1; Immune evasion
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Funding
- Hunan Provincial Department of Science and Technology (Provincial Science and Technology Innovation Platform and Talent Plan) Hunan Clinical Research Center of Traditional Chinese Medicine for Male Diseases [2018SK4012]
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Background We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. Methods The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8(+)T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8(+)T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. Results KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3 '-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8(+)T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8(+)T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. Conclusions LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.
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