Aberrant NEAT1_1 expression may be a predictive marker of poor prognosis in diffuse large B cell lymphoma

Article type: Research Article

Authors: Deng, Lan^{a; b; c; 1} | Jiang, Ling^{d; 1} | Tseng, Kuo-Fu^e | Liu, Yuan^c | Zhang, Xing^c | Dong, Ruihong^c | Lu, Zhigang^{c; *} | Wang, Xiuju^{a; b; *}

Affiliations: [a] Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China | [b] Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China | [c] Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China | [d] Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China | [e] Biophysics Department of Oregan State University, ALS-2139 Corvallis, OR 97330, USA

Correspondence: [*] Corresponding authors: Zhigang Lu, Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Xiuju Wang, Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road Yuexiu District of Guangzhou, Guangdong 510120, China, Tel.: +86 13710351276; E-mail: [email protected].

Note: [1] Lan Deng and Ling Jiang are the co-first authors.

Abstract: BACKGROUND: Many studies have demonstrated that the long non-coding RNA (lncRNA), NEAT1_1, plays critical roles in various human tumor entities and is related to the survival of patients with malignancies. However, the role of NEAT1_1 in diffuse large B cell lymphoma (DLBCL) remains unclear. The aim of this study was to investigate the role of NEAT1_1 in DLBCL. METHODS: The expression of NEAT1_1 was evaluated in paraffin-embedded tissues from 64 DLBCL patients and 15 lymphnoditis patients using the ISH method. The correlations between the expression levels of NEAT1_1 and clinical-pathological features and patients’ survival were also analyzed. After knocking down NEAT1_1 using shRNA in the DLBCL cell lines OCI-Ly1 and SUDHL-4, cell viability, apoptosis and migration were assessed by performing CCK8 assays, annexin V-FITC/PI double staining assays and migration filter assays, respectively. RESULTS: NEAT1_1 expression was increased in DLBCL tissue compared to lymphnoditis tissue samples (P< 0.001). The NEAT1_1 level was positively related to stage (P= 0.031), IPI (P= 0.017), extranodal site involvement (P= 0.042) and drug response (P= 0.040). Kaplan-Meier analysis showed that high expression levels of NEAT1_1 were correlated with a poor prognosis in DLBCL patients. After shRNA-NEAT1_1 was transfected into OCI-Ly1 and SUDHL-4 for 24 h, the NEAT1_1 level decreased to approximately one-third the level of the control. Moreover, the viability and migration ability of the DLBCL cell lines were significantly suppressed. shRNA-NEAT1_1 induced apoptosis in both DLBCL cell lines. CONCLUSIONS: Our results showed that NEAT1_1 plays an oncogenic role in DLBCL. NEAT1_1 expression may serve as a predictive marker for DLBCL patients.

Keywords: Diffuse large B cell lymphoma, long non-coding RNA, NEAT1_1

DOI: 10.3233/CBM-160221

Journal: Cancer Biomarkers, vol. 23, no. 2, pp. 157-164, 2018