Zhong Xing, Liu Zhiliang, Luo Qingfeng, Li Jingao, Zhang Weiwei, Shuang Yuerong
Department of Lymphatic and Hematological Oncology, Jiangxi Cancer Hospital (Affiliated Cancer Hospital of Nanchang University), Nanchang, Jiangxi 330006, P.R. China.
Department of Pathology, Jiangxi Cancer Hospital (Affiliated Cancer Hospital of Nanchang University), Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2021 Apr;21(4):245. doi: 10.3892/ol.2021.12506. Epub 2021 Feb 2.
Diffuse large B-cell lymphoma (DLBCL) is the most common and heterogeneous lymphoid malignancy. The subtype with MYC and BCL-2 double-expressor lymphoma (DEL) was defined by its aggressive nature and poor survival outcome. Therefore, the development of effective therapies for the DEL subtype is imperative. Fatty acid synthase (FASN) activity is associated with altered lipid metabolism and aberrant protein translation in DLBCL. However, the inter-regulation of these key processes is not fully determined in DEL. In the present study, the clinical and biological impact of FASN was investigated in the DEL subtype. Initially, FASN expression levels were analyzed from a patient cohort and the data indicated that the highest FASN expression was noted in DEL tissues compared with that noted in the DLBCL and reactive lymphoid hyperplasia tissues. Patients with DEL with combined high-FASN expression indicated poorer EFS outcomes than the rest of the patients. data indicated that FASN was overexpressed in SU-DHL-2 and U2932 cells. Silencing FASN decreased cell growth and promoted cell apoptosis by modulating the pERK/BCL-2 signaling pathway. In conclusion, the present study indicated that FASN was overexpressed in DEL and that its expression was associated with poor survival outcomes. Furthermore, the data demonstrated that FASN regulated the biological function via the pERK/BCL-2 signaling pathway. FASN serves a critical role in the progression of DEL and its expression may be associated with the development to a more aggressive phenotype of DLBCL. Therefore, it may be considered a potential therapeutic target for DLBCL.
弥漫性大B细胞淋巴瘤(DLBCL)是最常见且异质性的淋巴恶性肿瘤。具有MYC和BCL-2双表达淋巴瘤(DEL)的亚型因其侵袭性本质和较差的生存结果而被定义。因此,开发针对DEL亚型的有效疗法势在必行。脂肪酸合酶(FASN)活性与DLBCL中脂质代谢改变和异常蛋白质翻译相关。然而,在DEL中这些关键过程的相互调节尚未完全明确。在本研究中,对DEL亚型中FASN的临床和生物学影响进行了研究。最初,从患者队列中分析FASN表达水平,数据表明与DLBCL和反应性淋巴组织增生组织相比,DEL组织中FASN表达最高。具有高FASN联合表达的DEL患者的无事件生存期(EFS)结果比其他患者更差。数据表明FASN在SU-DHL-2和U2932细胞中过表达。沉默FASN通过调节pERK/BCL-2信号通路降低细胞生长并促进细胞凋亡。总之,本研究表明FASN在DEL中过表达,其表达与较差的生存结果相关。此外,数据表明FASN通过pERK/BCL-2信号通路调节生物学功能。FASN在DEL进展中起关键作用,其表达可能与DLBCL发展为更具侵袭性的表型相关。因此,它可能被认为是DLBCL的潜在治疗靶点。