circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of PD‐L1 through NF‐κB pathway

Abstract

Background: Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood. Methods: CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT-PCR, western blot, and other methods.Results: Among the thousands of circRNAs, 1238 circRNAs were significantly changed.As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_ circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_ circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa-circRNA3310-44, hsa_circ_0045746, hsa_circ_0016836, hsa-circRNA10899-9, hsa_ circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circ-CORO1C activated the NF-κB signaling pathway, increased P65 phosphorylation and upregulation of c-Myc and COX-2, leading to increased PD-L1 expression. Conclusion:CircCORO1C upregulates c-Myc and COX-2 through NF-κB signaling pathway, leading to the upregulation of PD-L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC. How to cite this article: Wu F, Sun G, Zheng W, et al. circCORO1C promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing the expression of

Circular RNAs in eukaryotic cells: origin, characteristics, mechanisms of molecular functioning in human malignant diseases

“…Wu и соавт. [352] исследовали онкогенный потенциал кольцевой РНК DLEU2 (circDLEU2), содержание микроРНК-496 и активируемой протеинкиназой циклического аденозинмонофосфата (цАМФ) каталитической субъединицы PRKACB микроРНК в опухолевых клетках ОМЛ. Установили, что уровень экспрессии кольцевой РНК circDLEU2 был повышен в тканях ОМЛ и способствовал пролиферации опухолевых клеток, при этом ингибировался клеточный апоптоз in vivo.…”

“…Кроме того, после дополнительных экспериментов было обнаружено, что повышенная экспрессия circDLEU2 существенно ингибирует экспрессию микроРНК-496, что способствует увеличению количества другой микроРНК. Это коллективное исследование показало, что повышенная экспрессия кольцевой РНК circDLEU2 усиливает развитие ОМЛ человека, за счет подавления микроРНК-496 и стимуляции экспрессии PRKACB микроРНК [352].…”

The current status and future of PD-L1 in liver cancer

“…In recent years, the effect of circRNAs mediated PD-L1 expression on the immune status of liver cancer has attracted much attention. Has-circ-0006852 (circCORO1C) promoted the development of HCC by activating the NF-κB signaling pathway, increasing the phosphorylation of P65, the expression of c-Myc, COX-2 and PD-L1 ( 158 ). Has-circ-0003288 acted as a miR-145 sponge and up-regulated PD-L1 expression through the PI3K/AKT signaling pathway, promoting EMT and HCC invasion ( 159 ).…”

The roles and mechanisms of circular RNAs related to mTOR in cancers

“…Multiple studies have shown that circRNAs are associated with the development and treatment of liver cancer. 52 Moreover, the activation of mTOR is considered to be an important event in the development of liver cancer. 53 CircC16orf62, hsa_circ_100,338, hsa_circ_0004001, hsa_circ_0004123, and hsa_circ_0075792 possess differential expression in HCC tissues and cells compared with adjacent normal tissues and cells and play the significant role of oncogenes when overexpressed in liver cancer.…”

“…Nevertheless, drug resistance and distant metastasis are remarkable obstacles to liver cancer treatment. Multiple studies have shown that circRNAs are associated with the development and treatment of liver cancer 52 . Moreover, the activation of mTOR is considered to be an important event in the development of liver cancer 53 .…”