Institute of Digestive Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Carcinogenesis. 2021 Apr 17;42(3):493-506. doi: 10.1093/carcin/bgaa138.
Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) has been reported to play an essential role in the development and progression of various human cancers. However, its expression pattern and possible mechanism in human hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we used western blot and immunohistochemical staining to detect protein expression. The effects of ANP32A on the proliferation, migration and invasion of HCC cells were examined using 5-ethynyl-20-deoxyuridine (EdU), colony formation, CCK-8, and transwell assays. RT-qPCR was performed to detect mRNA expression. The interaction between ANP32A and the high mobility group A1 (HMGA1) mRNA was assessed using RNA immunoprecipitation (RIP). The tumorigenicity of ANP32A was assessed by establishing a xenograft tumor model in Balb/c nude mice. We found that the ANP32A protein was expressed at high levels in patients with HCC, which was associated with a poor prognosis. Functional experiments revealed that the silencing of ANP32A inhibited the proliferation, migration, and invasion of HCC cells, whereas overexpression of ANP32A promoted these processes. Further investigations indicated that ANP32A bound the HMGA1 mRNA and maintained its stability to promote the expression of HMGA1, thereby increasing the expression and activation of STAT3. Finally, a xenograft tumor model of Balb/c nude mice confirmed the tumorigenicity of ANP32A. This study found that ANP32A is up-regulated in patients with HCC and may accelerate the proliferation, migration and invasion of HCC cells by modulating the HMGA1/STAT3 pathway.
酸性亮氨酸丰富核磷蛋白 32A（ANP32A）已被报道在各种人类癌症的发生和发展中发挥重要作用。然而，其在人肝细胞癌（HCC）中的表达模式和可能的机制仍有待阐明。在本研究中，我们使用 Western blot 和免疫组织化学染色来检测蛋白质表达。使用 5-乙炔基-20-脱氧尿苷（EdU）、集落形成、CCK-8 和 Transwell 测定来检测 ANP32A 对 HCC 细胞增殖、迁移和侵袭的影响。使用 RT-qPCR 检测 mRNA 表达。使用 RNA 免疫沉淀（RIP）评估 ANP32A 与高迁移率族蛋白 A1（HMGA1）mRNA 之间的相互作用。通过在 Balb/c 裸鼠中建立异种移植肿瘤模型来评估 ANP32A 的致瘤性。我们发现 ANP32A 蛋白在 HCC 患者中高表达，与预后不良相关。功能实验表明，沉默 ANP32A 抑制 HCC 细胞的增殖、迁移和侵袭，而过表达 ANP32A 则促进这些过程。进一步的研究表明，ANP32A 结合 HMGA1 mRNA 并维持其稳定性以促进 HMGA1 的表达，从而增加 STAT3 的表达和激活。最后，Balb/c 裸鼠异种移植肿瘤模型证实了 ANP32A 的致瘤性。这项研究发现，ANP32A 在 HCC 患者中上调，可能通过调节 HMGA1/STAT3 通路加速 HCC 细胞的增殖、迁移和侵袭。
