Hao Shunxin, Yao Zhi, Liu Yifeng
Department of General Surgery, Wuhan University of Science and Technology Hospital, Wuhan, Hubei, China.
Arch Med Sci. 2024 Jun 30;20(3):847-862. doi: 10.5114/aoms/171672. eCollection 2024.
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, posing a serious threat to the life of patients. This study aims to investigate the role of LINC00847 and the LINC00847/miR-455-3p/HDAC4 mechanism in PC progression.
The RNA levels of LINC00847, miR-455-3p and HDAC4 were determined by RT-qPCR. HDAC4 protein level was assessed by western blotting. Colony formation and CCK-8 assays were employed to test the proliferation of PC cells. Transwell and scratch assays were conducted to evaluate the cell invasive and migratory abilities, respectively. The effect of LINC00847 silencing on PC cells was verified using a mouse xenograft model. The correlation among LINC00847, miR-455-3p and HDAC4 was ascertained by dual-luciferase reporter (DLR) assay and Pearson's correlation analysis.
The result showed that LINC00847 mainly localized in the cytoplasm was upregulated in PC cells and tissues. Downregulating LINC00847 hindered migration, proliferation, and invasion of PC cells . Moreover, it also suppressed tumor growth in an xenograft model. LINC00847 was found to directly target miR-455-3p. miR-455-3p overexpression inhibited cell proliferation and invasion. In addition, HDAC4 was confirmed to be a target gene of miR-455-3p, and HDAC4 overexpression overturned the impact of LINC00847 knockdown on PC cell progression.
Our findings reveal that LINC00847 potentially plays a key role in the carcinogenesis of PC progression. This effect may be mediated via regulating the miR-455-3p/HDAC4 axis. This study provides insights into the intricate molecular mechanisms underlying PC and opens avenues for potential therapeutic interventions.
胰腺癌（PC）是消化系统常见的恶性肿瘤，对患者生命构成严重威胁。本研究旨在探讨LINC00847以及LINC00847/miR-455-3p/HDAC4机制在胰腺癌进展中的作用。
通过逆转录定量聚合酶链反应（RT-qPCR）测定LINC00847、miR-455-3p和HDAC4的RNA水平。采用蛋白质免疫印迹法评估HDAC4蛋白水平。采用集落形成实验和细胞计数试剂盒-8（CCK-8）实验检测胰腺癌细胞的增殖情况。分别采用Transwell实验和划痕实验评估细胞的侵袭和迁移能力。利用小鼠异种移植模型验证LINC00847沉默对胰腺癌细胞的影响。通过双荧光素酶报告基因（DLR）实验和Pearson相关性分析确定LINC00847、miR-455-3p和HDAC4之间的相关性。
结果显示，主要定位于细胞质的LINC00847在胰腺癌细胞和组织中表达上调。下调LINC00847可抑制胰腺癌细胞的迁移、增殖和侵袭。此外，它还抑制了异种移植模型中的肿瘤生长。发现LINC00847直接靶向miR-455-3p。miR-455-3p过表达抑制细胞增殖和侵袭。此外，证实HDAC4是miR-455-3p的靶基因，HDAC4过表达可逆转LINC00847敲低对胰腺癌细胞进展的影响。
我们的研究结果表明，LINC00847可能在胰腺癌进展的致癌过程中起关键作用。这种作用可能是通过调节miR-455-3p/HDAC4轴介导的。本研究为深入了解胰腺癌潜在的复杂分子机制提供了见解，并为潜在的治疗干预开辟了途径。
