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Upregulation of a novel LncRNA AC104958.2 stabilized by PCBP2 promotes proliferation and microvascular invasion in hepatocellular carcinoma
Experimental Cell Research ( IF 3.3 ) Pub Date : 2021-08-18 , DOI: 10.1016/j.yexcr.2021.112791
Zhili Ma 1 , Shun Li 2 , Yiqin Wang 2 , Jiaxing Zhang 2 , Xiaofang Zeng 2
Affiliation  

Long non-coding RNAs (lncRNAs) were reported to be involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Microvascular invasion (MVI) is an independent predictor for early recurrence and overall survival in postoperative patients with HCC. However, the mechanisms how lncRNAs affect HCC and MVI remain elusive. By RNA sequencing (RNA-seq) in a series of 65 HCC samples and 30 paired adjacent non-tumor liver tissue, we identified a novel lncRNA AC104958.2 that was significantly upregulated in HCC tissues and associated with MVI. Overexpression of AC104958.2 obviously elevated cell viability, metastasis, invasion and epithelial-mesenchymal transition (EMT), while knockout of AC104958.2 mediated by CRISPR/Cas9 technique showed the opposite effects. In addition, the interaction between AC104958.2 and Poly (rC) binding protein 2 (PCBP2) was identified by RNA pull down and mass spectrometry (MS), which was further validated by RNA immunoprecipitation (RIP). PCBP2 was also upregulated in HCC and associated with MVI. High expression of both AC104958.2 and PCBP2 was correlated with tumor size, TNM stage and MVI in HCC. Overexpression of PCBP2 greatly increased the cell viability, metastasis, invasion and EMT. Moreover, actinomycin D assay showed that overexpression of PCBP2 enhanced the RNA stability of AC104958.2. In conclusion, our study showed that a novel lncRNA AC104958.2 exerted oncogenic roles in HCC and might be a promising biomarker and therapeutic target.



中文翻译:

由 PCBP2 稳定的新型 LncRNA AC104958.2 的上调促进肝细胞癌的增殖和微血管侵袭

据报道,长链非编码 RNA (lncRNA) 与肝细胞癌 (HCC) 的肿瘤发生和进展有关。微血管侵犯 (MVI) 是 HCC 术后患者早期复发和总生存的独立预测因子。然而,lncRNA 如何影响 HCC 和 MVI 的机制仍然难以捉摸。通过在一系列 65 个 HCC 样本和 30 个配对的相邻非肿瘤肝组织中进行 RNA 测序 (RNA-seq),我们鉴定了一种新的 lncRNA AC104958.2,该 lncRNA AC104958.2 在 HCC 组织中显着上调并与 MVI 相关。AC104958.2 的过表达明显提高了细胞活力、转移、侵袭和上皮间质转化 (EMT),而 CRISPR/Cas9 技术介导的 AC104958.2 敲除显示出相反的效果。另外,AC104958之间的相互作用。2 和 Poly (rC) 结合蛋白 2 (PCBP2) 通过 RNA 下拉和质谱 (MS) 进行鉴定,并通过 RNA 免疫沉淀 (RIP) 进一步验证。PCBP2 在 HCC 中也上调并与 MVI 相关。AC104958.2 和 PCBP2 的高表达与 HCC 中的肿瘤大小、TNM 分期和 MVI 相关。PCBP2的过表达大大增加了细胞活力、转移、侵袭和EMT。此外,放线菌素 D 测定表明 PCBP2 的过表达增强了 AC104958.2 的 RNA 稳定性。总之,我们的研究表明,一种新的 lncRNA AC104958.2 在 HCC 中发挥致癌作用,可能是一个有前景的生物标志物和治疗靶点。PCBP2 在 HCC 中也被上调并与 MVI 相关。AC104958.2 和 PCBP2 的高表达与 HCC 中的肿瘤大小、TNM 分期和 MVI 相关。PCBP2的过表达大大增加了细胞活力、转移、侵袭和EMT。此外,放线菌素 D 测定表明 PCBP2 的过表达增强了 AC104958.2 的 RNA 稳定性。总之,我们的研究表明,一种新的 lncRNA AC104958.2 在 HCC 中发挥致癌作用,可能是一个有前景的生物标志物和治疗靶点。PCBP2 在 HCC 中也上调并与 MVI 相关。AC104958.2 和 PCBP2 的高表达与 HCC 中的肿瘤大小、TNM 分期和 MVI 相关。PCBP2的过表达大大增加了细胞活力、转移、侵袭和EMT。此外,放线菌素 D 测定表明 PCBP2 的过表达增强了 AC104958.2 的 RNA 稳定性。总之,我们的研究表明,一种新的 lncRNA AC104958.2 在 HCC 中发挥致癌作用,可能是一个有前景的生物标志物和治疗靶点。

更新日期:2021-08-24
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