长链非编码RNA（lncRNA）HOXB-AS3通过靶向miR-498-5p调控ADAM9的表达，从而促进子宫内膜癌细胞增殖并抑制其凋亡。
Long non-coding RNA (lncRNA) HOXB-AS3 promotes cell proliferation and inhibits apoptosis by regulating ADAM9 expression through targeting miR-498-5p in endometrial carcinoma.
作者信息
Xing Ying, Sun Xianhua, Li Feng, Jiang Xuan, Jiang Afang, Li Xiaofan, Lv Ruiting, Shao Liwei
机构信息
Department of General Medicine, Wulidun Neighborhood Community Health Service Center Affiliated with the Fifth Hospital of Wuhan, Wuhan, Hubei, China.
Department of Infectious Disease, Red Cross Society Hospital of Wuhan (Wuhan No.11 Hospital), Wuhan, Hubei, China.
出版信息
J Int Med Res. 2021 Jun;49(6):3000605211013548. doi: 10.1177/03000605211013548.
OBJECTIVE
Long non-coding RNA (lncRNA) expression is closely related to the pathogenesis and progression of various tumors. In this study, we investigated the mechanisms of lncRNA HOXB cluster antisense RNA 3 (HOXB-AS3), miRNA(miR)-498-5p, and disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) in endometrial carcinoma (EC) cells.
METHODS
The expression levels of lncRNA HOXB-AS3 in EC tissues and cells were detected using RT-qPCR assays. The effects of HOXB-AS3 knockdown on EC cell proliferation and apoptosis were measured using CCK-8 assays, colony formation assays, and flow cytometry. In addition, putative miR-498-5p binding sites were identified in HOXB-AS3 and ADAM9. The targeted relationships were further verified using dual-luciferase reporter and RNA pull-down assays.
RESULTS
HOXB-AS3 expression was upregulated in EC tissues and cells. EC cell proliferation and viability decreased significantly in HOXB-AS3 knockdown groups. A putative miR-498-5p binding site in HOXB-AS3 was verified. Inhibition of miR-498-5p rescued the effects of HOXB-AS3 knockdown on cell proliferation and apoptosis. Finally, ADAM9 was verified as a direct target gene of miR-498-5p.
CONCLUSIONS
Our results suggest that lncRNA HOXB-AS3 is highly expressed in EC tissues and cells. Downregulation of HOXB-AS3 inhibits cell proliferation and promotes apoptosis in EC cells. HOXB-AS3 can upregulate ADAM9 expression by sponging miR-498-5p.
目的
长链非编码RNA（lncRNA）表达与多种肿瘤的发病机制和进展密切相关。在本研究中，我们探讨了lncRNA HOXB簇反义RNA 3（HOXB-AS3）、微小RNA（miR）-498-5p和含去整合素和金属蛋白酶结构域蛋白9（ADAM9）在子宫内膜癌（EC）细胞中的作用机制。
方法
采用RT-qPCR检测EC组织和细胞中lncRNA HOXB-AS3的表达水平。采用CCK-8法、集落形成法和流式细胞术检测HOXB-AS3敲低对EC细胞增殖和凋亡的影响。此外，在HOXB-AS3和ADAM9中鉴定了假定的miR-498-5p结合位点。通过双荧光素酶报告基因和RNA下拉实验进一步验证靶向关系。
结果
HOXB-AS3在EC组织和细胞中表达上调。HOXB-AS3敲低组EC细胞增殖和活力显著降低。验证了HOXB-AS3中一个假定的miR-498-5p结合位点。抑制miR-498-5p可挽救HOXB-AS3敲低对细胞增殖和凋亡的影响。最后，验证ADAM9是miR-498-5p的直接靶基因。
结论
我们的结果表明，lncRNA HOXB-AS3在EC组织和细胞中高表达。HOXB-AS3的下调抑制EC细胞增殖并促进其凋亡。HOXB-AS3可通过海绵吸附miR-498-5p上调ADAM9表达。
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