敲低长链非编码 RNA DLX6-AS1 通过下调 PRR11 表达和上调 miR-144 抑制非小细胞肺癌细胞增殖、迁移和侵袭，促进细胞凋亡。

Knockdown of lncRNA DLX6-AS1 inhibits cell proliferation, migration and invasion while promotes apoptosis by downregulating PRR11 expression and upregulating miR-144 in non-small cell lung cancer.

机构信息

Department of Senile Respiratory and Sleep, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Department Two of Respiratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

Biomed Pharmacother. 2019 Jan;109:1851-1859. doi: 10.1016/j.biopha.2018.09.151. Epub 2018 Nov 26.

DOI:10.1016/j.biopha.2018.09.151

PMID:30551440

Abstract

BACKGROUND

Long non-coding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) was reported to be dysregulated in lung cancer. However, detailed roles of DLX6-AS1 in the pathogenesis of non-small cell lung cancer (NSCLC) were largely unknown.

METHODS

The expression of DLX6-AS1 was measured in NSCLC tissues and cells by quantitative real-time PCR (qRT-PCR). The abundance of proline rich 11 (PRR11) were detected by qRT-PCR and western blot, respectively. The effects of DLX6-AS1 and PRR11 on cell proliferation, migration, invasion and apoptosis were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell and flow cytometry analysis, respectively. Luciferase reporter assay, qRT-PCR and western blot were performed to confirm the interaction between miR-144 and DLX6-AS1 or PRR11. Tumor xenograft assay was performed to verify the role of DLX6-AS1 in NSCLC in vivo.

RESULTS

DLX6-AS1 and PRR11 were elevated in NSCLC tissues and cells. DLX6-AS1 was positively correlated with PRR11 mRNA expression in NSCLC tissues. Knockdown of DLX6-AS1 and PRR11 significantly suppressed cell proliferation, migration and invasion and induced apoptosis in NSCLC cells, which was reversed by PRR11 overexpression. In addition, DLX6-AS1 and PRR11 were demonstrated to interact with microRNA-144 (miR-144) and DLX6-AS1 upregulated PRR11 expression by acting as a competing endogenous RNA (ceRNA) of miR-144 in NSCLC cells. Furthermore, DLX6-AS1 knockdown suppressed tumor growth in NSCLC in vivo by upregulating miR-144 and downregulating PRR11.

CONCLUSION

Knockdown of DLX6-AS1 inhibited cell proliferation, migration, invasion and promoted apoptosis by downregulating PRR11 expression and upregulating miR-144 in NSCLC.

摘要

背景

长链非编码 RNA（lncRNA）远端同源盒 6 反义 1（DLX6-AS1）在肺癌中被报道失调。然而，DLX6-AS1 在非小细胞肺癌（NSCLC）发病机制中的详细作用在很大程度上尚不清楚。

方法

通过实时定量 PCR（qRT-PCR）测量 NSCLC 组织和细胞中的 DLX6-AS1 表达。通过 qRT-PCR 和 Western blot 分别检测脯氨酸丰富 11（PRR11）的丰度。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐（MTT）、Transwell 和流式细胞术分析分别研究 DLX6-AS1 和 PRR11 对细胞增殖、迁移、侵袭和凋亡的影响。荧光素酶报告分析、qRT-PCR 和 Western blot 用于证实 miR-144 与 DLX6-AS1 或 PRR11 之间的相互作用。肿瘤异种移植实验用于验证 DLX6-AS1 在体内 NSCLC 中的作用。

结果

DLX6-AS1 和 PRR11 在 NSCLC 组织和细胞中升高。DLX6-AS1 与 NSCLC 组织中 PRR11 mRNA 表达呈正相关。DLX6-AS1 和 PRR11 的敲低显着抑制 NSCLC 细胞的增殖、迁移和侵袭，并诱导细胞凋亡，而过表达 PRR11 则逆转了这一作用。此外，还证实了 DLX6-AS1 和 PRR11 与 microRNA-144（miR-144）相互作用，并且 DLX6-AS1 通过充当 NSCLC 细胞中 miR-144 的竞争性内源性 RNA（ceRNA）而上调 PRR11 的表达。此外，DLX6-AS1 敲低通过上调 miR-144 和下调 PRR11 抑制 NSCLC 体内肿瘤生长。