研究动态
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长链非编码RNA RPLP0P2 通过miR-129-5p/锌指蛋白和BTB结构域蛋白20轴路促进结直肠癌的增殖和侵袭。

LncRNA RPLP0P2 Promotes Colorectal Cancer Proliferation and Invasion via the miR-129-5p/Zinc Finger and BTB Domain-Containing 20 Axis.

发表日期:2023 Aug 31
作者: Hang Yuan, Peng Yu, Zi-Ang Wan, Bing-Chen Chen, Shi-Liang Tu
来源: Cellular & Molecular Immunology

摘要:

我们先前报道了长链非编码RNA(lncRNA)RPLP0P2在结直肠癌(CRC)进展中的参与,然而它在CRC中的分子机制仍不清楚。在本研究中,我们观察到RPLP0P2在CRC组织和细胞系中上调表达。细胞活力通过MTT和克隆形成实验测定。迁移和侵袭能力通过伤口愈合、透过法和免疫荧光实验监测。结果显示RPLP0P2下调抑制了CRC细胞的细胞活力、迁移和侵袭能力,伴随着PCNA、N-钙黏蛋白和Vimentin表达下调以及E-钙黏蛋白表达上调。我们通过DIANA在线数据库确定miR-129-5p是RPLP0P2的下游靶点。事实上,RPLP0P2与miR-129-5p共定位,作为miR-129-5p的海绵。miR-129-5p抑制几乎消除了RPLP0P2抑制在CRC细胞中诱导的抗肿瘤效应。在CRC细胞中,酞锌和BTB结构域包含20(ZBTB20)被确定为miR-129-5p的一个潜在下游靶点。ZBTB20过表达在CRC细胞中预防了miR-129-5p模拟器介导的抗肿瘤效应。通过肿瘤异种移植实验来监测RPLP0P2在肿瘤生长中的作用。值得注意的是,在携带肿瘤的小鼠中,RPLP0P2沉默抑制了肿瘤生长,随之miR-129-5p表达增加,ZBTB20表达下降。我们的结果表明lncRNA RPLP0P2作为一个促进CRC细胞增殖和侵袭的癌基因,通过调节miR-129-5p/ZBTB20轴,因此可能作为CRC介入治疗的候选靶点。© 2023. 作者,独家许可Springer Science+Business Media, LLC,Springer Nature的一部分。
We previously reported that long non-coding RNA (lncRNA) RPLP0P2 is involved in the progression of colorectal cancer (CRC); however, its molecular mechanisms in CRC remain unclear. In this study, we observed that RPLP0P2 was upregulated in CRC tissues and cell lines. Cell viability was measured using the MTT and colony formation assays. Migration and invasion capabilities were monitored by wound healing, transwell, and immunofluorescence assays. The results showed that RPLP0P2 downregulation inhibited cell viability, migration, and invasion capabilities of CRC cells, accompanied by decreased PCNA, N-cadherin, and Vimentin, and increased E-cadherin expression. Using the DIANA online database, miR-129-5p was identified as a downstream target of RPLP0P2. In fact, RPLP0P2 colocalized with miR-129-5p, acting as a miR-129-5p sponge. MiR-129-5p-inhibition almost abrogated the anti-tumor effects induced by RPLP0P2 inhibition in CRC cells. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential downstream target of miR-129-5p in CRC cells. ZBTB20 overexpression prevented miR-129-5p mimic-mediated anti-tumor effects in CRC cells. A tumor xenograft assay was performed to monitor the role of RPLP0P2 in tumor growth. Of note, in tumor-bearing mice, RPLP0P2-silencing inhibited tumor growth, followed by increased miR-129-5p and decreased ZBTB20 expression. Our results suggest that lncRNA RPLP0P2 functions as an oncogene that promotes CRC cell proliferation and invasion via regulating the miR-129-5p/ZBTB20 axis, thus, it may serve as a candidate target for CRC interventional therapies.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.