Department of Ultrasound, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China.
Department of Magnetic Resonance Imaging, the Second Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161006, China.
World J Surg Oncol. 2022 Jun 16;20(1):203. doi: 10.1186/s12957-022-02655-6.
This study aimed to explore the specific pathogenesis of lncRNA MALAT1 promoting the invasion and metastasis of hepatocellular carcinoma (HCC) through peripheral blood vessels by regulating the expression of miRNA-613 molecule.
The data of 60 HCC metastatic patients and 60 HCC non-metastatic patients detected by the contrast-enhanced ultrasound (CEUS) in the Second Affiliated Hospital of Qiqihar Medical College from January 2020 to June 2021 were collected, as well as postoperatively retained HCC tissues and paired paracancer tissues (5 cm laterally from the edge of the cancer area), to study the changes of microangiogenesis in HCC tissues with CEUS. The correlation between CEUS grading and lncRNA MALAT1 in patients with HCC was analyzed through Pearson correlation analysis, lncRNA MALAT1 and miRNA-613 in HCC tissues of patients with HCC were detected by qRT-PCR, followed by the bioinformatic analysis for the relationship between lncRNA MALAT1 and miRNA-613. The Log-growing human HCC cell strain, HepG2, was selected for experiments. Adenovirus transfection knocked down lncRNA MALAT1 in HCC cells, which was divided into two groups (inhibitor-NC group and lncR-inhibitor group), followed by knocking down miRNA-613 on the basis of knocking down lncRNA MALAT1, which was divided into three groups (inhibitor-NC group, lncR-inhibitor groups, and lncR/miR613-inhibitor group). The expression of miRNA-613 and lncRNA MALAT1 in each group was detected by qRT-PCR. The migration and invasiveness of cells in each group were detected by Transwell assay.
CEUS of HCC and Pearson correlation analysis showed that CEUS grading and lncRNA MALAT1 were positively correlated in patients with HCC. In HCC tissues of patients with HCC, lncRNA MALAT1 expressed high and miRNA-613 expressed low. The results of bioinformatic analysis showed the targeting of lncRNA MALAT1 and miRNA-613. Knocking down lncRNA MALAT1 could increase miRNA-613 expression significantly, and reduce the migration of HCC cells. Inhibiting miRNA-613 based on knocking down lncRNA MALAT1 could increase the survival and migration of HCC cells.
lncRNA MALAT1 can promote HCC metastasis through the peripheral vascular infiltration by inhibiting the level of MiRNA-613, which can, therefore, be used as a potential target for the treatment of HCC.
本研究旨在通过调节 miRNA-613 分子的表达,探讨长链非编码 RNA(lncRNA)MALAT1 通过外周血管促进肝癌(HCC)侵袭和转移的具体发病机制。
收集 2020 年 1 月至 2021 年 6 月在齐齐哈尔医学院第二附属医院经超声造影(CEUS)检测的 60 例转移性 HCC 患者和 60 例非转移性 HCC 患者的数据,以及术后保留的 HCC 组织和配对癌旁组织(癌区边缘外侧 5cm),研究 HCC 组织中微脉管生成的变化。通过 Pearson 相关性分析分析 HCC 患者的 CEUS 分级与 lncRNA MALAT1 的相关性,通过 qRT-PCR 检测 HCC 患者 HCC 组织中 lncRNA MALAT1 和 miRNA-613 的表达,然后进行生物信息学分析 lncRNA MALAT1 与 miRNA-613 的关系。选择对数生长期人 HCC 细胞株 HepG2 进行实验。腺病毒转染敲低 HCC 细胞中的 lncRNA MALAT1,分为两组(抑制剂-NC 组和 lncR-抑制剂组),在此基础上敲低 lncRNA MALAT1 上的 miRNA-613,分为三组(抑制剂-NC 组、lncR-抑制剂组和 lncR/miR613-抑制剂组)。通过 qRT-PCR 检测各组中 miRNA-613 和 lncRNA MALAT1 的表达,通过 Transwell 实验检测各组细胞的迁移和侵袭。
HCC 的 CEUS 和 Pearson 相关性分析表明,HCC 患者的 CEUS 分级与 lncRNA MALAT1 呈正相关。在 HCC 患者的 HCC 组织中,lncRNA MALAT1 表达高,miRNA-613 表达低。生物信息学分析结果显示 lncRNA MALAT1 与 miRNA-613 的靶向关系。敲低 lncRNA MALAT1 可显著增加 miRNA-613 的表达,并减少 HCC 细胞的迁移。基于敲低 lncRNA MALAT1 抑制 miRNA-613 可增加 HCC 细胞的存活和迁移。
lncRNA MALAT1 可通过抑制 miRNA-613 水平促进 HCC 转移,可作为治疗 HCC 的潜在靶点。