Zai Hongyan, Wu Xin, Zhou Yifan, Hu Yu, Zhu Qin
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Appl Biochem Biotechnol. 2025 Jan;197(1):1-18. doi: 10.1007/s12010-024-05008-z. Epub 2024 Aug 2.
Long non-coding RNAs (Lnc RNAs) are proven to participate in liver cancer (LC) regulation. The regulation of miR-21 by lnc NBAT1 has been studied in other cancers. However, the effect of this regulation on LC and its specific mechanism remains unclear. Lnc NBAT1 and miR-21 expressions in clinical tissues were measured by RT-qPCR. PDCD4, AP-1, p-c-Fos, p-c-Jun, and cyclin D1 expressions were analyzed by Western blot. Overexpression of lnc NBAT1 was studied to explore its influence on malignant behaviors of Bel7402 cells and the development of LC in the xenograft mouse model (XMM). The regulation mechanism of lnc NBAT1 in LC was explored by lnc NBAT1 overexpression, miR-21 mimic treatment, or PDCD4 silencing in Bel7402 cells. Lnc NBAT1 expression was downregulated while miR-21 expression was upregulated in LC tissues and cell lines. In comparison with LX-2 cells, the expressions of PDCD4 and AP-1 were downregulated in Bel7402 cells, while those of p-c-Fos, p-c-Jun, and cyclin D1 were upregulated. Further, lnc NBAT1 was found to localize primarily in the cytoplasm of Bel7402 cells. Overexpression of lnc NBAT1 enhanced cell apoptosis, blocked the cell cycle, suppressed malignant behaviors of Bel7402 cells, and inhibited tumor progression in the XMM. Mechanistically, lnc NBAT1 functioned as a competing endogenous RNA (ceRNA) by binding to the downstream target miR-21 to stabilize the expressions of PDCD4 and AP-1, thereby inhibiting malignant behaviors of Bel7402 cells. Lnc NBAT1 suppressed malignant behaviors of LC cells through the miR-21/PDCD4/AP-1 axis. Lnc NBAT1 might be a promising biomarker for LC treatment.
长链非编码RNA（Lnc RNAs）已被证实参与肝癌（LC）的调控。lnc NBAT1对miR-21的调控在其他癌症中已有研究。然而，这种调控对肝癌的影响及其具体机制仍不清楚。通过RT-qPCR检测临床组织中lnc NBAT1和miR-21的表达。通过蛋白质免疫印迹法分析PDCD4、AP-1、p-c-Fos、p-c-Jun和细胞周期蛋白D1的表达。研究lnc NBAT1的过表达以探讨其对Bel7402细胞恶性行为及异种移植小鼠模型（XMM）中肝癌发展的影响。通过在Bel7402细胞中过表达lnc NBAT1、miR-21模拟物处理或PDCD4沉默来探索lnc NBAT1在肝癌中的调控机制。在肝癌组织和细胞系中，lnc NBAT1表达下调而miR-21表达上调。与LX-2细胞相比，Bel7402细胞中PDCD4和AP-1的表达下调，而p-c-Fos、p-c-Jun和细胞周期蛋白D1的表达上调。此外，发现lnc NBAT1主要定位于Bel7402细胞的细胞质中。lnc NBAT1的过表达增强细胞凋亡，阻断细胞周期，抑制Bel7402细胞的恶性行为，并抑制XMM中的肿瘤进展。机制上，lnc NBAT1作为竞争性内源RNA（ceRNA），通过与下游靶点miR-21结合来稳定PDCD4和AP-1的表达，从而抑制Bel7402细胞的恶性行为。lnc NBAT1通过miR-21/PDCD4/AP-1轴抑制肝癌细胞的恶性行为。lnc NBAT1可能是肝癌治疗的一个有前景的生物标志物。
