| Title | The nociceptin receptor promotes autophagy through NF-kB signaling and is transcriptionally regulated by E2F1 in HCC |
| Authors | Zhou, Xiaoshuang Chen, Dongtai Yan, Yan Li, Qiang Xing, Wei Liu, Yanling Chen, Yonghua Wang, Dongyin Yuan, Yunfei Xie, Jingdun Zeng, Weian Pan, Jiahao |
| Affiliation | Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Anesthesiol,State Key Lab Oncol South China, Guangzhou 510060, Peoples R China Huizhou Municipal Cent Hosp, Dept Anesthesiol, Huizhou 516001, Peoples R China Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Anesthesiol & Operating Theatre,State Key La, Guangzhou 510060, Peoples R China Peking Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518000, Peoples R China Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Dept Hepatobiliary Oncol,State Key Lab Oncol Sout, Guangzhou 510060, Peoples R China |
| Keywords | COLORECTAL-CANCER METASTASIS SUPPRESSES CELLS DETERMINES EXPRESSION JTC-801 GROWTH NUMBER |
| Issue Date | 5-Apr-2022 |
| Publisher | CELL DEATH DISCOVERY |
| Abstract | Opioids and their receptors are involved in cancer progression. However, the roles of the nociceptin receptor (NOP) and its antagonist (JTC801) in hepatocellular carcinoma (HCC) are poorly understood. The prognostic value of NOP expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HCC cohort. The biological role and mechanism of NOP in HCC tumor growth were determined in vitro and in vivo. We found that NOP was associated with the clinicopathological features and survival outcomes of HCC patients. NOP overexpression promoted HCC growth in vitro and in vivo. Mechanistically, NOP activated NF-kB signaling to promote autophagy, which inhibited apoptosis, in HCC cells. An inhibitor of autophagy, 3-MA, and an inhibitor of NF-kB, JSH-23, attenuated the function of NOP in HCC. E2F1 was identified as a transcription factor of NOP. The oncogenic role of NOP was positively regulated by E2F1. Furthermore, JTC801, a selective antagonist of NOP, abolished the function of NOP by inhibiting NF-kB signaling and autophagy. Our study demonstrates that NOP is an oncogene in HCC. We provide a potential therapeutic candidate and prognostic predictor for HCC. JTC801 could become a potential drug for HCC therapy. |
| URI | http://hdl.handle.net/20.500.11897/641990 |
| DOI | 10.1038/s41420-022-00978-7 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
