Lv Chao, Chen Guannan, Lv Shuang
Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China.
Hepatological Surgery Department, Tianjin First Central Hospital, Tianjin, China.
PeerJ. 2024 Dec 24;12:e18693. doi: 10.7717/peerj.18693. eCollection 2024.
CLP36 is also known as PDZ and LIM Domain 1 (PDLIM1) that is a ubiquitously-expressed α-actinin-binding cytoskeletal protein involved in carcinogenesis, and our current study aims to explore its involvement in lymphoma.
Accordingly, the CLP36 expression pattern in lymphoma and its association with the overall survival was predicted. Then, qPCR was applied to gauge CLP36 expression in lymphoma cells and determine the knockdown efficiency. The survival, proliferation and apoptosis of CLP36-silencing lymphoma cells were tested. Cell viability, proliferation and apoptosis were assessed based on cell counting kit-8 (CCK-8) assay, colony formation assay, EdU staining, and flow cytometry, respectively. Additionally, qPCR was used to calculate the expressions of proteins associated with metastasis and apoptosis, while immunoblotting was employed to determine the phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/cAMP-response element binding protein (CREB).
CLP36 expression was relatively higher in lymphoma, which was associated with a poor prognosis. Also, CLP36 was highly-expressed in lymphoma cells and the silencing of CLP36 contributed to the suppressed survival and proliferation as well as the enhanced apoptosis of lymphoma cells. Further, CLP36 silencing repressed the expressions of Cadherin 2 (CDH2) and Vimentin (VIM) yet promoted those of Bax and Caspase 3 in lymphoma cells, concurrent with the reduction on the phosphorylation of PI3K, AKT and CREB, all of which were confirmed to be positively correlated with CLP36.
This study, so far as we are concerned, provided evidence on the involvement of CLP36/PI3K/AKT/CREB axis in lymphoma, which may be contributive for the identification on the relevant molecular targets of lymphoma.
CLP36也被称为PDZ和LIM结构域1（PDLIM1），是一种广泛表达的与α-辅肌动蛋白结合的细胞骨架蛋白，参与致癌过程，我们目前的研究旨在探讨其在淋巴瘤中的作用。
据此，预测CLP36在淋巴瘤中的表达模式及其与总生存期的关联。然后，应用qPCR检测淋巴瘤细胞中CLP36的表达并确定敲低效率。检测CLP36沉默的淋巴瘤细胞的生存、增殖和凋亡情况。分别基于细胞计数试剂盒-8（CCK-8）检测、集落形成检测、EdU染色和流式细胞术评估细胞活力、增殖和凋亡。此外，使用qPCR计算与转移和凋亡相关的蛋白表达，同时采用免疫印迹法测定磷酸肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化状态。
CLP36在淋巴瘤中的表达相对较高，这与预后不良相关。此外，CLP36在淋巴瘤细胞中高表达，CLP36的沉默导致淋巴瘤细胞的生存和增殖受到抑制以及凋亡增强。进一步研究发现，CLP36沉默抑制了淋巴瘤细胞中钙黏蛋白2（CDH2）和波形蛋白（VIM）的表达，但促进了Bax和半胱天冬酶3的表达，同时PI3K、AKT和CREB的磷酸化水平降低，所有这些均被证实与CLP36呈正相关。
就我们所知，本研究提供了CLP36/PI3K/AKT/CREB轴参与淋巴瘤的证据，这可能有助于识别淋巴瘤的相关分子靶点。
