Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6

IF 2.1 4区 生物学 Q4 CELL BIOLOGY Histochemistry and Cell Biology Pub Date : 2024-04-13 DOI:10.1007/s00418-024-02275-z
Feifei Chen, Juan Chen, Yuan Yuan, Surong Fang, Jing Xie, Xiaojuan Xu, Zhenhua Yang, Jianzhong Jiang
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Abstract

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

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Circ_100549 通过上调 BIRC6 促进肺腺癌的肿瘤进展
肺腺癌(LUAD)是肺癌的一种亚型,在全球的发病率和死亡率都很高。新的证据表明,环状 RNA(circRNA)在人类癌症(包括肺腺癌)中发挥着关键作用。据报道,循环RNA_100549(circ_100549)在非小细胞肺癌(NSCLC)样本中显著上调,但其在调控LUAD进展中的作用仍有待探索。本研究旨在探讨 circ_100549 在 LUAD 中的功能作用及其下游分子机制。首先,我们发现 circ_100549 在 LUAD 细胞系中表达较高。功能缺失实验证实,circ_100549的缺失抑制了LUAD细胞的增殖,但加速了细胞的凋亡。此外,体内实验证明,沉默 circ_100549 可抑制肿瘤生长。随后,在数据库分析的基础上,我们进行了一系列实验,包括RNA结合蛋白免疫沉淀(RIP)、RNA/DNA牵引、荧光素酶报告和染色质免疫沉淀(ChIP)实验,以探索circ_100549在LUAD进展中的作用机制。结果表明,circ_100549作为一种ceRNA,通过海绵状miR-95-5p上调BPTF的表达,从而在转录水平上上调LUAD中BIRC6的表达。总之,我们的研究表明,circ_100549通过上调BIRC6的表达促进了LUAD的进展。
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来源期刊
Histochemistry and Cell Biology
Histochemistry and Cell Biology 生物-细胞生物学
CiteScore
4.90
自引率
8.70%
发文量
112
审稿时长
1 months
期刊介绍: Histochemistry and Cell Biology is devoted to the field of molecular histology and cell biology, publishing original articles dealing with the localization and identification of molecular components, metabolic activities and cell biological aspects of cells and tissues. Coverage extends to the development, application, and/or evaluation of methods and probes that can be used in the entire area of histochemistry and cell biology.
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