环状 RNA circ-LDLRAD3 通过 miR-137-3p/PTN 轴下调抑制胰腺癌进展。
Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.
机构信息
Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China; The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China.
Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China; The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, Henan Province, China.
出版信息
Life Sci. 2019 Dec 15;239:116871. doi: 10.1016/j.lfs.2019.116871. Epub 2019 Sep 12.
Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.
新兴证据表明，环状 RNA（circRNAs）的失调与癌症进展密切相关。在本文中，我们专注于探索 circ-LDLRAD3 在胰腺癌中的功能作用。使用定量逆转录聚合酶链反应和 Western blot 测定基因表达。应用细胞计数试剂盒-8 和 5-乙炔基-2'-脱氧尿苷测定法评估 PANC-1 和 SW1990 细胞的增殖。通过划痕愈合试验和 Transwell 侵袭试验评估 PANC-1 和 SW1990 细胞的迁移和侵袭。进行荧光素酶报告基因测定进行靶标验证。结果表明，circ-LDLRAD3 在胰腺癌组织和细胞系中过表达。circ-LDLRAD3 的表达增加表明胰腺癌患者的预后不良。circ-LDLRAD3 的敲低抑制了体外和体内胰腺癌的生长。miR-137-3p 被鉴定为 circ-LDLRAD3 的直接靶标。更重要的是，circ-LDLRAD3 的上调可以减轻 miR-137-3p 对胰腺癌细胞增殖、迁移和侵袭的抑制作用。此外，circ-LDLRAD3 可以通过 miR-137-3p 调节多效蛋白（PTN）的表达。总之，circ-LDLRAD3 的敲低通过 miR-137-3p/PTN 轴抑制胰腺癌细胞的增殖、迁移和侵袭，为胰腺癌的进展提供了新的机制。
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