LncRNA UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on anaplastic thyroid carcinoma via miR-148a/PD-L1 pathway.

BACKGROUND

LncRNAs play an important role in the regulation of the killing effect of cytotoxic CD8 + T cells in various cancers. However, the role and underlying mechanisms of UCA1 in the killing effect of cytotoxic CD8 + T cells in anaplastic thyroid carcinoma (ATC) are not clear.

METHODS

UCA1, miR-148a, and PD-L1 expression were detected by quantitative real-time PCR and/or Western blot. The ratio of PD-L1ATC cells/ATC cells was determined using flow cytometry. The ability of CD8 + T cells to kill target ATC cells was detected by Chromium-51 (Cr) release assay. The targeted relationship between UCA1 and miR-148a was confirmed by dual-luciferase reporter gene assay.

RESULTS

UCA1 and PD-L1 expression levels were elevated in ATC tissues and cells. Silencing UCA1 and PD-L1 enhanced the killing effect of cytotoxic CD8 + T cells on ATC cells. UCA1 negatively regulated the expression of miR-148a, and miR-148a targeted PD-L1 to down-regulate its expression. Besides, we found that UCA1 attenuated the killing effect of cytotoxic CD8 + T cells and reduced cytokine secretion through PD-L1 and miR-148a. Finally, silencing UCA1 or PD-L1 in ATC cells restored the suppression of the killing effect of CD8 + T cells in vivo.

CONCLUSION

UCA1 attenuated the killing effect of cytotoxic CD8 + T cells on ATC cells through the miR-148a/PD-L1 pathway.