Circ-HMGA2 (hsa_circ_0027446) promotes the metastasis and epithelial-mesenchymal transition of lung adenocarcinoma cells through the miR-1236-3p/ZEB1 axis.

Circ-HMGA2 (hsa_circ_0027446) promotes the metastasis and epithelial-mesenchymal transition of lung adenocarcinoma cells through the miR-1236-3p/ZEB1 axis.
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Circ-HMGA 2(hsa_circ_0027446)通过miR-1236- 3 p/ZEB 1轴促进肺腺癌细胞的转移和上皮-间质转化。

DOI:
10.1038/s41419-021-03601-2
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发表时间:
2021-03-24
影响因子:
9
通讯作者:
Zheng Y
Zheng Y
中科院分区:
生物学1区
文献类型:
--
作者:
Yu Z;Zhu X;Li Y;Liang M;Liu M;Liu Z;Qin L;Wu X;Du K;Liu L;Wang Y;Zheng Y

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肺腺癌(LUAD)在世界范围内具有较高的发病率和死亡率,但其详细的分子病理学尚不清楚。虽然circRNA已逐渐被确定为在肿瘤中差异表达并在肿瘤进展中起关键作用的分子,但其在LUAD中的作用知之甚少。通过微阵列分析,我们获得了LUAD的circRNA表达谱,发现circ-HMGA 2(hsa_circ_0027446),一种新的RNA,在LUAD中高表达。在36对LUAD及癌旁正常组织中进一步证实了circ-HMGA 2的高表达。在功能上,circ-HMGA 2促进体外和体内LUAD细胞转移。荧光素酶报告基因分析和FISH结果显示,circ-HMGA 2与miR-1236- 3 p相互作用,miR-1236- 3 p与ZEB 1相互作用。此外,miR-1236- 3 p在LUAD中以低水平表达,抑制LUAD细胞转移,并抑制circ-HMGA 2的功能。ZEB 1是一种EMT促进转录因子。PCR和WB分析结果表明,circ-HMGA 2促进ZEB 1表达和EMT。miR-1236- 3 p具有相反的作用,逆转了circ-HMGA 2对EMT的促进作用。总之,circ-HMGA 2通过miR-1236- 3 p/EMT轴促进LUAD细胞转移,表明其可能是LUAD的治疗靶点。
Lung adenocarcinoma (LUAD) has high incidence and mortality rates worldwide; however, its detailed molecular pathology remains unclear. Although circRNAs have gradually been identified as molecules that are differentially expressed in tumors and play key roles in tumor progression, their role in LUAD is poorly understood. Through microarray analysis, we obtained the circRNA expression profile of LUAD and found that circ-HMGA2 (hsa_circ_0027446), a novel RNA, is highly expressed in LUAD. The high expression of circ-HMGA2 was further verified in 36 paired LUAD and adjacent normal tissues. Functionally, circ-HMGA2 promoted LUAD cell metastasis in vitro and in vivo. The luciferase reporter assay and FISH results showed that circ-HMGA2 interacts with miR-1236-3p and that miR-1236-3p interacts with ZEB1. In addition, miR-1236-3p was expressed at low levels in LUAD, inhibited LUAD cell metastasis, and suppressed the function of circ-HMGA2. ZEB1 is an EMT-promoting transcription factor. The PCR and WB analysis results showed that circ-HMGA2 promotes both ZEB1 expression and EMT. MiR-1236-3p had the opposite effect, reversing the promotive effect of circ-HMGA2 on EMT. In summary, circ-HMGA2 promotes LUAD cell metastasis through the miR-1236-3p/EMT axis, indicating that it could be a therapeutic target in LUAD.
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