miR-205-5p 通过靶向 TNFAIP8 抑制皮肤癌细胞增殖并增加药物敏感性。
MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8.
机构信息
Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia Hui Autonomous Region, China.
Julius L. Chambers Biomedical Biotechnology Research Institute (BBRI), North Carolina Central University, 1801 Fayetteville St., Durham, NC, 27707, USA.
出版信息
Sci Rep. 2021 Mar 11;11(1):5660. doi: 10.1038/s41598-021-85097-6.
Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3'UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAF mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.
肿瘤坏死因子-α诱导蛋白 8（TNFAIP8）是 TIPE/TNFAIP8 家族的一员，该家族调节肿瘤的生长和存活。我们的目标是描绘 TNFAIP8 在皮肤癌发展和进展中的详细致癌作用。在这里，我们证明了 TNFAIP8 的高表达与基底细胞癌（BCC）、鳞状细胞癌（SCC）和黑色素瘤患者组织中的发展有关。TNFα 诱导的 TNFAIP8 表达或在 SCC 或黑色素瘤细胞系中外源表达 TNFAIP8 导致细胞生长/增殖增加。相反，TNFAIP8 的沉默降低了皮肤癌细胞的存活/细胞迁移。我们还表明，miR-205-5p 靶向 TNFAIP8 的 3'UTR 并抑制 TNFAIP8 的表达。此外，miR-205-5p 下调了 TNFAIP8 介导的细胞自噬，增加了对 B-RAF 突变激酶抑制剂 vemurafenib 的敏感性，并诱导黑色素瘤细胞凋亡。总之，我们的数据表明，miR-205-5p 通过靶向 TNFAIP8 作为皮肤癌中的肿瘤抑制因子发挥作用。
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