LINC01234/MicroRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells (Retracted article. See vol. 31, pg. 14, 2023)
LINC01234/MicroRNA-31-5p/MAGEA3 Axis Mediates the Proliferation and Chemoresistance of Hepatocellular Carcinoma Cells (Retracted article. See vol. 31, pg. 14, 2023)
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DOI：
10.1016/j.omtn.2019.10.035
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发表时间：
2020-03-06
期刊：
影响因子：
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通讯作者：
Fu, Binsheng
中科院分区：
文献类型：
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作者：
Chen, Yunhao;Zhao, Hui;Fu, Binsheng
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有侵袭性强、预后差的特点，其发病机制尚不清楚。基于癌症基因组图谱（TCGA）数据库的分析，黑素瘤相关抗原A3（MAGEA 3）和长链非编码RNA（lncRNA）LINC 01234在HCC中上调，并且与HCC的不良预后相关。我们研究了MAGEA 3和LINC 01234如何影响HCC细胞功能和顺铂耐药的机制。MAGEA 3耗竭抑制体外HepG 2细胞和Huh 7细胞的增殖、侵袭和顺铂耐药性，降低耐药相关蛋白2（MRP 2）、MRP 3和多药耐药蛋白1（MDR-1）表达，并升高ALB表达。RNA下拉和RIP测定鉴定了LINC 01234和MAGEA 3与microRNA-31- 5 p（miR-315 p）的结合。LINC 01234可通过与miR-31- 5 p结合来恢复MAGEA 3的表达。此外，我们将质粒递送到HepG 2细胞和Huh 7细胞中以改变LINC 01234和miR-31- 5 p的表达。下调miR-31- 5 p可增强HepG 2和Huh 7细胞的增殖和侵袭能力，抑制顺铂诱导的细胞凋亡，而LINC 01234的敲除可减弱miR-31- 5 p的缺失所引起的效应。总之，这些数据突出了MAGEA 3/LINC 01234/miR-31- 5 p轴在HCC进展和HCC细胞的化学抗性中的重要作用。
Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by aggressiveness and poor prognosis; however, the molecular mechanism remains to be fully identified. Based on the analysis of The Cancer Genome Atlas (TCGA) database, melanoma-associated antigen A3 (MAGEA3) and long noncoding RNA (lncRNA) LINC01234 were upregulated in HCC and associated with poor prognosis of HCC. We investigated the mechanism of how MAGEA3 and LINC01234 influenced HCC cellular functions and cisplatin resistance. MAGEA3 depletion inhibited proliferation, invasion, and cisplatin resistance of HepG2 cells and Huh7 cells in vitro, reduced resistance-associated protein 2 (MRP2), MRP3, and multidrug resistance protein 1 (MDR-1) expression, and elevated ALB expression. RNA pull-down and RIP assays identified the binding of LINC01234 and MAGEA3 to microRNA-31-5p (miR-315p). LINC01234 could restore MAGEA3 expression by binding to miR-31-5p. Furthermore, we delivered plasmids into HepG2 cells and Huh7 cells to alter the expression of LINC01234 and miR-31-5p. When miR-31-5p was downregulated, the proliferation and invasion of HepG2 cells and Huh7 cells were enhanced and the cisplatin-induced apoptosis was inhibited, while LINC01234 knockdown could diminish the effects caused by miR-31-5p depletion. In summary, these data highlight the vital role of MAGEA3/LINC01234/miR-31-5p axis in the HCC progression and chemoresistance of HCC cells.