TERC is a lncRNA with 451nt that functions as the template for telomerase during telomere lengthening. Several studies showed that TERC also functions as a lncRNA independent of telomerase, such as anti-apoptosis and regulates DNA damage response (Gazzaniga and Blackburn, 2014; Ting et al., 2009). Recently, Dr. Haiying Liu and her colleagues from Sun Yat-Sen University published their work “TERC Suppresses PD-L1 Expression by Downregulating RNA Binding Protein HuR” on SCIENCE CHINA Life Sciences, and reveals that TERC is able to suppress PD-L1 expression independent of telomerase in cancer cells.
The telomeres in cancer cells are lengthened in two ways, one is by telomerase, the other is by the alternative pathway of telomere lengthening (ALT). The ALT cancers are more aggressive and malignant than telomerase positive cancers with unknown mechanism. In their study, Liu’s group compared the TERC and PD-L1 expression levels in three pairs of ALT/telomerase cancer cells from non-small cell lung cancer, osteosarcoma and neuroblastoma respectively, and found that the TERC is low whereas PD-L1 is high in ALT cells, which probably facilitates ALT cancer immune escape.
Mechanistically, TERC accelerates PD-L1 mRNA degradation by inhibiting the expression of HuR, which binds to the 3’UTR of PD-L1 mRNA and stabilized it. By survival analysis using clinical data from database, they revealed that breast cancer patients with high TERC level display good prognosis during chemotherapy. In addition, they enhanced TERC expression using a small molecule, AS1842856, and inhibited PD-L1 elevation in cells treated with chemotherapy drug. Altogether, this research reveals a novel function of TERC in PD-L1 inhibition and makes it a promising candidate for avoid cancer immune escape during chemotherapy.
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TERC Suppresses PD-L1 Expression by Downregulating RNA Binding Protein HuR
Science China Life Sciences