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LINC00908通过下调miR-671-5p促进弥漫性大B细胞淋巴瘤发展。

LINC00908 Promotes Diffuse Large B-Cell Lymphoma Development by Down-Regulating miR-671-5p.

作者信息

Zeng Hong, Wei Yongqiang, Wei Xiaolei, Feng Ru

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Apr 30;13:3589-3599. doi: 10.2147/CMAR.S299715. eCollection 2021.

Abstract

INTRODUCTION

Emerging evidence has revealed that long noncoding RNA (lncRNA) play important role in almost all kinds of human cancers. LINC00908 has been reported to be involved in the development of prostate cancer, colorectal cancer and gastric cancer which was functioned as an oncogene. However, the potential biology role and molecular mechanism of LINC00908 in diffuse large B-cell lymphoma are still unclear.

METHODS

LINC00908 and miR-671-5p expression were evaluated in DLBCL tissues and cell lines using RT-qPCR. CCK-8 and transwell assay were used to analyze the in vitro role of LINC00908 in DLBCL progression. The xenograft model was used to explore the in vivo role of LINC00908 in DLBCL growth. The physical interaction between LINC00908 and miR-671-5p was confirmed using bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down.

RESULTS

The expression of LINC00908 was markedly up-regulated in diffuse large B-cell lymphoma tissues and cell lines, and the decreased expression of LINC00908 significantly inhibited diffuse large B-cell lymphoma cell proliferation and invasion. Then, we revealed that LINC00908 directly interacted with miR-671-5p, which was down-regulated in diffuse large B-cell lymphoma cells and highly expressed with LINC00908 knockdown. Moreover, luciferase reporter assays and RNA immunoprecipitation (RIP) assay further proved that miR-671-5p is a direct target of LINC00908 in diffuse large B-cell lymphoma cells. Rescue experiments were also performed, and we confirmed that LINC00908 acts as an oncogene role in diffuse large B-cell lymphoma through miR-671-5p. Finally, the influence of LINC00908 silence significantly inhibited diffuse large B-cell lymphoma growth in vivo.

CONCLUSION

LINC00908 promotes malignancy of diffuse large B-cell lymphoma through regulating miR-671-5p.

摘要

引言

新出现的证据表明,长链非编码RNA(lncRNA)在几乎所有类型的人类癌症中都发挥着重要作用。据报道,LINC00908参与前列腺癌、结直肠癌和胃癌的发展,其作用为癌基因。然而,LINC00908在弥漫性大B细胞淋巴瘤中的潜在生物学作用和分子机制仍不清楚。

方法

使用RT-qPCR评估弥漫性大B细胞淋巴瘤组织和细胞系中LINC00908和miR-671-5p的表达。采用CCK-8和Transwell实验分析LINC00908在弥漫性大B细胞淋巴瘤进展中的体外作用。异种移植模型用于探索LINC00908在弥漫性大B细胞淋巴瘤生长中的体内作用。使用生物信息学分析、双荧光素酶实验、RNA免疫沉淀(RIP)和RNA下拉实验证实LINC00908与miR-671-5p之间的物理相互作用。

结果

LINC00908在弥漫性大B细胞淋巴瘤组织和细胞系中的表达明显上调,LINC00908表达的降低显著抑制弥漫性大B细胞淋巴瘤细胞的增殖和侵袭。然后,我们发现LINC00908直接与miR-671-5p相互作用,miR-671-5p在弥漫性大B细胞淋巴瘤细胞中表达下调,在LINC00908敲低时高表达。此外,荧光素酶报告实验和RNA免疫沉淀(RIP)实验进一步证明miR-671-5p是弥漫性大B细胞淋巴瘤细胞中LINC00908的直接靶点。还进行了挽救实验,我们证实LINC00908通过miR-671-5p在弥漫性大B细胞淋巴瘤中发挥癌基因作用。最后,LINC00908沉默的影响显著抑制了弥漫性大B细胞淋巴瘤在体内的生长。

结论

LINC00908通过调节miR-671-5p促进弥漫性大B细胞淋巴瘤的恶性发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3912/8096343/f60e60c3a210/CMAR-13-3589-g0001.jpg

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