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藏红花酸通过下调肿瘤促进子 miR-122-5p 和上调肿瘤抑制因子 FOXP2 和 SPRY2 抑制乳腺癌细胞增殖。

Crocin suppresses breast cancer cell proliferation by down-regulating tumor promoter miR-122-5p and up-regulating tumor suppressors FOXP2 and SPRY2.

机构信息

Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China.

Department of Endocrinology, Nanshi Hospital Affiliated to Henan University, Nanyang, Henan, 473065, China.

出版信息

Environ Toxicol. 2023 Jul;38(7):1597-1608. doi: 10.1002/tox.23789. Epub 2023 Mar 29.

DOI:10.1002/tox.23789
PMID:36988377
Abstract

Crocin has been reported to have antitumor activity in several tumors including breast cancer. Nevertheless, the mechanism of action of crocin on breast cancer remains unclear. The cytotoxicity of crocin was evaluated by CCK-8 assay. Cell proliferation was assessed using EdU incorporation assay and western blot analysis. Breast cancer-related genes were extracted from GEPIA. miR-122-5p targets were predicted using Targetscan, starbase, and miRDB softwares. Luciferase reporter assay was employed to confirm whether miR-122-5p targeted sprouty2 (SPRY2) and forkhead box P2 (FOXP2). Results showed that crocin exhibited cytotoxicity and suppressed the proliferation in breast cancer cells. miR-122-5p was upregulated in breast cancer tissues and cells. Crocin suppressed miR-122-5p to block the proliferation of breast cancer cells. Seven targets of miR-122-5p were identified in breast cancer. SPRY2 and FOXP2 were selected for further experiments due to their involvement in breast cancer. miR-122-5p targeted SPRY2 and FOXP2 to inhibit their expression. miR-122-5p knockdown restrained breast cancer cell proliferation by targeting SPRY2 and FOXP2. Additionally, crocin increased SPRY2 and FOXP2 expression by inhibiting miR-122-5p expression. Together, our results suggested that crocin inhibited proliferation of breast cancer cells through decreasing miR-122-5p expression and the subsequent increase of SPRY2 and FOXP2 expression.

摘要

西红花苷已被报道在多种肿瘤中具有抗肿瘤活性,包括乳腺癌。然而,西红花苷对乳腺癌的作用机制尚不清楚。通过 CCK-8 法评估西红花苷的细胞毒性。通过 EdU 掺入试验和 Western blot 分析评估细胞增殖。从 GEPIA 提取乳腺癌相关基因。使用 Targetscan、starbase 和 miRDB 软件预测 miR-122-5p 的靶标。采用荧光素酶报告实验验证 miR-122-5p 是否靶向 Sprouty2 (SPRY2) 和 Forkhead box P2 (FOXP2)。结果表明,西红花苷具有细胞毒性,并抑制乳腺癌细胞的增殖。miR-122-5p 在乳腺癌组织和细胞中上调。西红花苷抑制 miR-122-5p 以阻断乳腺癌细胞的增殖。在乳腺癌中鉴定出 miR-122-5p 的 7 个靶标。由于 SPRY2 和 FOXP2 参与乳腺癌,因此选择它们进行进一步实验。miR-122-5p 靶向 SPRY2 和 FOXP2 以抑制其表达。miR-122-5p 敲低通过靶向 SPRY2 和 FOXP2 抑制乳腺癌细胞增殖。此外,西红花苷通过抑制 miR-122-5p 的表达增加 SPRY2 和 FOXP2 的表达。总之,我们的结果表明,西红花苷通过降低 miR-122-5p 的表达和随后增加 SPRY2 和 FOXP2 的表达来抑制乳腺癌细胞的增殖。

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