Mesh : Animals Female Humans Male Mice Actin-Related Protein 3 / metabolism genetics Apoptosis Carcinoma, Pancreatic Ductal / pathology metabolism genetics Cell Line, Tumor Cell Movement Cell Proliferation Epithelial-Mesenchymal Transition / genetics Gene Expression Regulation, Neoplastic Mice, Inbred BALB C Mice, Nude Osteopontin / metabolism genetics Pancreatic Neoplasms / pathology metabolism genetics Prognosis RNA, Long Noncoding / genetics metabolism

来  源:   DOI:10.1038/s41419-024-06876-3   PDF(Pubmed)

Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment methods. Long non-coding RNAs (lncRNAs) have been found involved in tumorigenic and progression. The present study revealed that LINC01133, a fewly reported lncRNA, was one of 16 hub genes that could predict PDAC patients\' prognosis. LINC01133 was over-expressed in PDAC tumors compared to adjacent pancreas and could promote PDAC proliferation and metastasis in vitro and in vivo, as well as inhibit PDAC apoptosis. LINC01133 expression positively correlated to secreted phosphoprotein 1 (SPP1) expression, leading to an enhanced epithelial-mesenchymal transition (EMT) process. LINC01133 bound with actin-related protein 3 (Arp3), the complex reduced SPP1 mRNA degradation which increased SPP1 mRNA level, ultimately leading to PDAC proliferation. This research revealed a novel mechanism of PDAC development and provided a potential prognosis indicator that may benefit PDAC patients.
摘要:
胰腺导管腺癌(PDAC)是一种治疗方法有限的致死性疾病。已发现长链非编码RNA(lncRNA)与肿瘤的发生和进展有关。本研究表明,LINC01133,一种鲜有报道的lncRNA,是可以预测PDAC患者预后的16个hub基因之一。与邻近胰腺相比,LINC01133在PDAC肿瘤中过表达,可以促进PDAC的体外和体内增殖和转移,以及抑制PDAC细胞凋亡。LINC01133表达与分泌型磷蛋白1(SPP1)表达呈正相关,导致增强的上皮-间质转化(EMT)过程。LINC01133与肌动蛋白相关蛋白3(Arp3)结合,复合物减少了SPP1mRNA的降解,从而增加了SPP1mRNA的水平,最终导致PDAC增殖。这项研究揭示了PDAC发展的新机制,并提供了可能使PDAC患者受益的潜在预后指标。
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