LINC00857 contributes to proliferation and lymphomagenesis by regulating miR-370-3p/CBX3 axis in diffuse large B-cell lymphoma

Abstract

Abstract 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.