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藏红花酸通过 miR-320a/ATG2B 对皮肤鳞状细胞癌发挥抗增殖和促凋亡作用。

Crocin exerts anti-proliferative and apoptotic effects on cutaneous squamous cell carcinoma via miR-320a/ATG2B.

机构信息

Department of Dermatology, Zibo Central Hospital, Zibo, China.

Department of Gynecology, Affiliated Qingdao Central Hospital, Qingdao University, Qingdao, China.

出版信息

Bioengineered. 2021 Dec;12(1):4569-4580. doi: 10.1080/21655979.2021.1955175.

Abstract

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent skin malignancy, and the effective therapy still remains a challenge. Crocin can be used for cSCC therapy. This study explored the effects of cSCC cells treatment with crocin in vitro and in vivo. The study used A431 and SCL-1 cells lines, cSCC human samples and BALB/C nude mice for investigations. Apoptosis was determined by MTT assays, while miR-320a and ATG2B expressions were validated through RT-qPCR. Interaction of miR-320a with ATG2B was examined via dual luciferase reporter assay. The autophagy and apoptosis proteins expressions were further confirmed through western blot and immunofluorescence staining assays. The results indicated a significantly upregulated miR-320a, but a down-regulated ATG2B expression in the cSCC clinical samples. Crocin significantly repressed cSCC cells growth, and induced apoptosis through autophagy. Furthermore, miR-320a expression was inhibited and ATG2B expression was increased. Dual luciferase reporter assay revealed that miR-320a regulated ATG2B expression directly. Additionally, the upregulation of ATG2B expression in cSCC cells inhibited cell proliferation and led to cell apoptosis. Crocin also reduced tumor growth and stimulated the apoptosis in vivo. In conclusion, miR-320a is upregulated and ATG2B is down-regulated in cSCC, Crocin suppresses the proliferation and induces apoptosis of cSCC cells. Further, Crocin increases autophagy while miR-320a hinders autophagy and the apoptotic effects of crocin on cSCC cells. MiR-320a binds ATG2B directly, and ATG2B expression is upregulated by crocin. Finally, Crocin triggers cSCC cells apoptosis in vivo. Crocin can target ATG2B/miR-320a and may be an effective alternative for cSCC treatment.

摘要

皮肤鳞状细胞癌 (cSCC) 是一种高发的皮肤恶性肿瘤,有效的治疗方法仍然是一个挑战。藏红花酸可用于治疗 cSCC。本研究探讨了藏红花酸在体外和体内对 cSCC 细胞的作用。该研究使用 A431 和 SCL-1 细胞系、cSCC 人样本和 BALB/C 裸鼠进行研究。通过 MTT 测定法确定细胞凋亡,通过 RT-qPCR 验证 miR-320a 和 ATG2B 的表达。通过双荧光素酶报告基因检测法检测 miR-320a 与 ATG2B 的相互作用。通过 Western blot 和免疫荧光染色法进一步确认自噬和细胞凋亡蛋白的表达。结果表明,cSCC 临床样本中 miR-320a 表达显著上调,而 ATG2B 表达下调。藏红花酸显著抑制 cSCC 细胞生长,并通过自噬诱导细胞凋亡。此外,miR-320a 的表达受到抑制,ATG2B 的表达增加。双荧光素酶报告基因检测法表明,miR-320a 直接调控 ATG2B 的表达。此外,cSCC 细胞中 ATG2B 表达的上调抑制细胞增殖并导致细胞凋亡。藏红花酸还减少了肿瘤的生长并刺激了体内的细胞凋亡。总之,miR-320a 在 cSCC 中上调,ATG2B 下调,藏红花酸抑制 cSCC 细胞的增殖并诱导细胞凋亡。此外,藏红花酸增加自噬,而 miR-320a 抑制自噬和藏红花酸对 cSCC 细胞的凋亡作用。miR-320a 直接与 ATG2B 结合,藏红花酸上调 ATG2B 的表达。最后,藏红花酸在体内引发 cSCC 细胞凋亡。藏红花酸可以靶向 ATG2B/miR-320a,可能是治疗 cSCC 的有效替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbad/8806488/72278c66fc5d/KBIE_A_1955175_UF0001_OC.jpg

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