National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Department of Lymphatic and Hematologic Oncology, Jiangxi Cancer Hospital, Nanchang City, Jiangxi Province, China.
Carcinogenesis. 2021 May 28;42(5):733-741. doi: 10.1093/carcin/bgab013.
Diffuse large B-cell lymphoma (DLBCL) remains to be a high aggressive and invasive malignancy with enigmatic etiology. Ectopic expression of long non-coding RNAs is widely involved in the progression of human cancers. We discovered that LINC00857 level was remarkably elevated in DLBCL tissues compared with non-tumor controls. High LINC00857 level predicts lower survival rate, more advanced tumor node metastasis and larger tumor size. LINC00857 overexpression promoted DLBCL cell proliferation and facilitated cell cycle as evidenced by elevated Cyclin D1 and proliferating cell nuclear antigen (PCNA) accompanying with reduced p21 level. LINC00857 overexpression also suppressed DLBCL cell apoptosis as evidenced by elevated Bcl-2 protein level, reduced Bax and cleaved caspase-3 protein levels. On the contrary, LINC00857 knockdown using short hairpin RNAs inhibited DLBCL cell proliferation yet induced cell apoptosis. LINC00857 knockdown also repressed tumor growth in vivo, concomitant with decreased Ki67 level. Besides, microRNA miR-370 was down-regulated in DLBCL tissues and served as a competitive endogenous RNA (ceRNA) target of LINC00857. We further validated that chromobox homolog 3 (CBX3) served as a downstream target gene of miR-370-3p. LINC00857 level was reversely correlated with miR-370-3p level yet positively correlated with CBX3 level. In addition, CBX3 overexpression alleviated the impact of LINC00857 knockdown on DLBCL cell survival. In conclusion, our findings indicated that LINC00857 contributes to DLBCL proliferation and lymphomagenesis through regulating miR-370-3p/CBX3 axis.
弥漫性大 B 细胞淋巴瘤 (DLBCL) 仍然是一种具有神秘病因的高侵袭性和高侵略性恶性肿瘤。长链非编码 RNA 的异位表达广泛涉及人类癌症的进展。我们发现，与非肿瘤对照相比，DLBCL 组织中的 LINC00857 水平显著升高。高 LINC00857 水平预示着较低的生存率、更晚期的肿瘤淋巴结转移和更大的肿瘤大小。LINC00857 过表达促进了 DLBCL 细胞的增殖，并通过升高细胞周期蛋白 D1 和增殖细胞核抗原 (PCNA) 以及降低 p21 水平来促进细胞周期。LINC00857 过表达还抑制了 DLBCL 细胞的凋亡，表现为 Bcl-2 蛋白水平升高、Bax 和 cleaved caspase-3 蛋白水平降低。相反，使用短发夹 RNA 敲低 LINC00857 抑制了 DLBCL 细胞的增殖，却诱导了细胞凋亡。LINC00857 敲低也抑制了体内肿瘤的生长，同时降低了 Ki67 水平。此外，miR-370 在 DLBCL 组织中下调，并作为 LINC00857 的竞争性内源性 RNA (ceRNA) 靶标。我们进一步验证了 chromobox homolog 3 (CBX3) 是 miR-370-3p 的下游靶基因。LINC00857 水平与 miR-370-3p 水平呈负相关，与 CBX3 水平呈正相关。此外，CBX3 过表达缓解了 LINC00857 敲低对 DLBCL 细胞存活的影响。总之，我们的研究结果表明，LINC00857 通过调节 miR-370-3p/CBX3 轴促进 DLBCL 的增殖和淋巴瘤的发生。
