Circular RNA circCSNK1G3 induces HOXA10 signaling and promotes the growth and metastasis of lung adenocarcinoma cells through hsa-miR-143-3p sponging,Cellular Oncology

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Circular RNA circCSNK1G3 induces HOXA10 signaling and promotes the growth and metastasis of lung adenocarcinoma cells through hsa-miR-143-3p sponging
Cellular Oncology ( IF 4.9 ) Pub Date : 2020-10-29 , DOI: 10.1007/s13402-020-00565-x
Tong Lu ₁ , Tong Qiu ₁ , Bin Han ₁ , Yuanyong Wang ₁ , Xiao Sun ₁ , Yi Qin ₁ , Ao Liu ₁ , Nan Ge ₁ , Wenjie Jiao ₁

Affiliation

Background

In the last decade, a relatively novel, ubiquitous and highly stable subclass of non-coding RNAs, called circular (circ)-RNAs, has increasingly been implicated in cancer development, and several of them have been shown to act as microRNA sponges. As yet, however, the role of circRNAs in lung adenocarcinoma (LUAD) development has largely remained unexplored.

Methods

Bioinformatics, microarray-based and qRT-PCR expression assays were used to assess circRNA, miRNA and mRNA expression in LUAD patient samples and cell lines. siRNA-mediated silencing was used to assess the effect of circCSNK1G3 on various LUAD-associated characteristics such as proliferation, migration, invasion and tumorigenesis, both in vitro and in vivo. Western blotting, immunohistochemistry, fluorescence in situ hybridization (FISH) and luciferase reporter activity assays were used to characterize relationships between circCSNK1G3, miR-143-3p and HOXA10 in LUAD cells.

Results

By screening for differentially expressed circRNAs, we found that circCSNK1G3 was aberrantly expressed in primary LUAD tissues and cell lines. An oncogenic role of circCSNK1G3 was deduced from its aberrant expression and associated enhancement of LUAD A549 and H1299 cell proliferation, migration and invasion. We also found that circCSNK1G3 can directly interact with and suppress miR-143-3p expression by serving as a ‘miR-143-3p sponge’. In addition, we found that circCSNK1G3 can modulate homeobox (HOX) A10 expression through miR-143-3p signaling and, thereby, affect LUAD tumorigenesis.

Conclusions

Our data indicate that circCSNK1G3 can induce HOXA10 expression and, thereby, promote the growth and metastasis of LUAD cells through hsa-miR-143-3p sponging. As such, our data highlight the targetability of the circCSNK1G3/miR-143-3p/HOXA10 signaling axis in patients with LUAD.

中文翻译：

环状RNA circCSNK1G3诱导HOXA10信号传导并通过hsa-miR-143-3p海绵作用促进肺腺癌细胞的生长和转移

背景

在过去的十年中，一种相对新颖、普遍存在且高度稳定的非编码 RNA 亚类，称为环状 (circ)-RNA，越来越多地与癌症的发展有关，其中一些已被证明可以充当 microRNA 海绵。然而，迄今为止，circRNA 在肺腺癌 (LUAD) 发展中的作用在很大程度上仍未得到探索。

方法

使用生物信息学、基于微阵列和 qRT-PCR 表达测定来评估 LUAD 患者样本和细胞系中的 circRNA、miRNA 和 mRNA 表达。使用 siRNA 介导的沉默来评估 circCSNK1G3 对体外和体内各种 LUAD 相关特征（如增殖、迁移、侵袭和肿瘤发生）的影响。使用蛋白质印迹、免疫组织化学、荧光原位杂交 (FISH) 和荧光素酶报告基因活性测定来表征 LUAD 细胞中 circCSNK1G3、miR-143-3p 和 HOXA10 之间的关系。

结果

通过筛选差异表达的circRNA，我们发现circCSNK1G3在原代LUAD组织和细胞系中异常表达。 circCSNK1G3 的致癌作用是根据其异常表达以及相关的 LUAD A549 和 H1299 细胞增殖、迁移和侵袭增强来推断的。我们还发现 circCSNK1G3 可以通过充当“miR-143-3p 海绵”直接与 miR-143-3p 相互作用并抑制 miR-143-3p 表达。此外，我们发现circCSNK1G3可以通过miR-143-3p信号调节同源框（HOX）A10的表达，从而影响LUAD肿瘤发生。