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环状 RNA circ-LRP6 促进食管鳞状细胞癌中 Myc 驱动的肿瘤发生。

Circular RNA circ-LRP6 facilitates Myc-driven tumorigenesis in esophageal squamous cell cancer.

机构信息

Department of Radiation Oncology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University , Huai'an, Jiangsu, China.

出版信息

Bioengineered. 2020 Dec;11(1):932-938. doi: 10.1080/21655979.2020.1809922.

Abstract

Circular RNA (circRNA) circ-LRP6 was recently proven to be a pivotal player in various human diseases. Nevertheless, its role in esophageal squamous cell cancer (ESCC) remains unknown. In the current study, we investigated the expression level, biological function and mechanism of circ-LRP6 in ESCC. Circ-LRP6 was significantly upregulated in ESCC tissues and correlated with malignant clinicopathological characteristics and poor prognosis. Knockdown of circ-LRP6 evidently reduced ESCC cell viability, colony formation and invasion. Circ-LRP6 was mainly located in the cytoplasm and could sponge miR-182 to increase the expression of Myc, a well-documented proto-oncogene. Importantly, circ-LRP6 depletion significantly retarded tumor growth . And silencing of miR-182 or overexpression of Myc effectively rescued the attenuated aggressive phenotype of ESCC cells caused by circ-LRP6 knockdown. Therefore, our data indicate that circ-LRP6 is a novel oncogenic circRNA in ESCC, targeting the circ-LRP6/miR-182/Myc signaling may be a promising therapeutic approach for ESCC patients.

摘要

环状 RNA (circRNA) circ-LRP6 最近被证明在各种人类疾病中起着关键作用。然而,其在食管鳞状细胞癌 (ESCC) 中的作用尚不清楚。在本研究中,我们研究了 circ-LRP6 在 ESCC 中的表达水平、生物学功能和机制。circ-LRP6 在 ESCC 组织中显著上调,并与恶性临床病理特征和不良预后相关。circ-LRP6 的敲低显著降低了 ESCC 细胞的活力、集落形成和侵袭能力。circ-LRP6 主要位于细胞质中,可以海绵 miR-182 来增加已被证实的原癌基因 Myc 的表达。重要的是,circ-LRP6 的缺失显著抑制了肿瘤的生长。沉默 miR-182 或过表达 Myc 可有效挽救 circ-LRP6 敲低引起的 ESCC 细胞侵袭表型减弱。因此,我们的数据表明 circ-LRP6 是 ESCC 中的一种新型致癌 circRNA,靶向 circ-LRP6/miR-182/Myc 信号通路可能是 ESCC 患者有前途的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634b/8291805/1af0dbff642c/KBIE_A_1809922_UF0001_OC.jpg

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