BBOX1-AS1 Activates Hedgehog Signaling Pathway to Facilitate the Proliferation and Stemness of Esophageal Squamous Cell Carcinoma Cells via miR-506-5p/EIF5A/PTCH1 Axis.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467216666230130132927

Liya Hu, Hong Cao, Lijun Zheng, Ruichao Li

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引用次数: 1

Abstract

Aims and objective: This study aimed to unveil the specific function of lncRNA BBOX1 antisense RNA 1 (BBOX1-AS1) in ESCC cells and the underlying regulatory mechanism.

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly disease. Molecular mechanisms essential to ESCC development and progression require in-depth investigation. Long noncoding RNAs (lncRNAs) have been suggested as crucial effectors in modulating tumor growth.

Methods: RT-qPCR and western blot examined the expression of genes and proteins of concern, respectively. Colony formation and EdU assays assessed the changes in cell proliferation. Sphere formation assay also detected the stemness of ESCC cells. Bioinformatics prediction, along with mechanistic assays (FISH, Subcellular fractionation, RNA pull-down, RIP, and luciferase reporter), was conducted to explore the gene interactions and regulatory relationship.

Results: BBOX1-AS1 was observed to be aberrantly up-regulated in ESCC tissues and cell lines. BBOX1-AS1 depletion exerted suppressive impacts on ESCC cell proliferation and stemness, while BBOX1-AS1 overexpression led to the opposite consequences. Moreover, BBOX1-AS1 was verified to activate Hedgehog signaling pathway via up-regulating PTCH1, and BBOX1-AS1 could sponge miR-506-5p to up-regulate EIF5A, thus stabilizing PTCH1 mRNA. Rescue experiments indicated that BBOX1-AS1 could affect ESCC cell proliferation and stemness via modulation on PTCH1.

Conclusion: To conclude, BBOX1-AS1 activates Hedgehog signaling pathway to facilitate the proliferation and stemness of ESCC cells via miR-506-5p/EIF5A/PTCH1 axis.

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BBOX1-AS1通过miR-506-5p/EIF5A/PTCH1轴激活Hedgehog信号通路促进食管鳞状细胞癌细胞的增殖和干性

目的与目的:本研究旨在揭示lncRNA BBOX1反义RNA 1 (BBOX1- as1)在ESCC细胞中的具体功能及其调控机制。背景:食管鳞状细胞癌(ESCC)是一种致命疾病。ESCC发生和发展的分子机制需要深入研究。长链非编码rna (lncRNAs)被认为是调节肿瘤生长的关键效应物。方法:RT-qPCR和western blot分别检测相关基因和蛋白的表达情况。菌落形成和EdU测定评估细胞增殖的变化。球形成法检测ESCC细胞的干性。生物信息学预测以及机制分析(FISH、亚细胞分离、RNA下拉、RIP和荧光素酶报告)被用于探索基因相互作用和调控关系。结果:BBOX1-AS1在ESCC组织和细胞系中异常上调。BBOX1-AS1缺失对ESCC细胞增殖和干性具有抑制作用，而BBOX1-AS1过表达则导致相反的结果。此外，BBOX1-AS1通过上调PTCH1激活Hedgehog信号通路，BBOX1-AS1可以海绵miR-506-5p上调EIF5A，从而稳定PTCH1 mRNA。挽救实验表明BBOX1-AS1可能通过调控PTCH1影响ESCC细胞的增殖和干性。结论:综上所述，BBOX1-AS1通过miR-506-5p/EIF5A/PTCH1轴激活Hedgehog信号通路，促进ESCC细胞的增殖和干细胞化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.