与PIWIL1相互作用的RNA piR-017724通过沉默PLIN3抑制增殖、侵袭和迁移，并抑制肝癌的发展。
PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3.
作者信息
Wu Yi-Jing, Wang Jie, Zhang Peng, Yuan Liu-Xia, Ju Lin-Ling, Wang Hui-Xuan, Chen Lin, Cao Ya-Li, Cai Wei-Hua, Ni Yi, Li Min
机构信息
Medical School of Nantong University, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, China.
Nantong Institute of Liver Disease, Department of Hepatobiliary Surgery, Nantong Third People's Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, China.
出版信息
Front Oncol. 2023 Jul 11;13:1203821. doi: 10.3389/fonc.2023.1203821. eCollection 2023.
BACKGROUND
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited.
METHODS
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases.
RESULTS
The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3.
CONCLUSIONS
Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.
背景
肝细胞癌（HCC）占原发性肝癌的大多数。在全球范围内，肝癌是癌症相关死亡的第四大常见原因。最近的研究发现，PIWI相互作用RNA（piRNA）参与各种肿瘤的发生和发展，并且与恶性肿瘤的生长、侵袭、转移及预后密切相关。关于piRNA在HCC发生发展中的作用及功能机制的研究有限。
方法
采用定量逆转录-聚合酶链反应（qRT-PCR）检测piR-017724在HCC组织和细胞中的表达。基于HCC患者的临床资料，进一步分析piR-017724的临床及预后价值。然后，在HCC细胞中对piR-017724进行靶向沉默和过表达，以研究piR-017724的生物学功能。此外，通过高通量测序和公共数据库预测并验证piR-017724的下游靶蛋白。
结果
piR-017724在HCC组织和细胞中显著下调，且piR-017724的下调与HCC的肿瘤分期及不良预后相关。piR-017724抑制剂促进HCC细胞的增殖、迁移和侵袭，而piR-017724模拟物则有相反作用。然而，piR-017724不影响HCC细胞的凋亡。高通量测序和qRT-PCR证实了piR-017724与PLIN3之间的相互关系。因此，我们推测piR-017724可能通过影响下游蛋白PLIN3来抑制HCC的发生发展。
结论
我们的研究表明，在HCC中低表达的piR-017724可抑制HCC细胞的增殖、迁移和侵袭，并可能通过PLIN3影响肝细胞癌的发展，这为piR-017724在肝细胞癌治疗中的临床应用提供了新的见解。
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