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芥子氰酸硫苷通过抑制 KRT6A/S100A2 轴发挥抗结直肠癌作用。

Sinapine thiocyanate exhibited anti-colorectal cancer effects by inhibiting KRT6A/S100A2 axis.

机构信息

Transformation Engineering Research Center of Chronic Disease Diagnosis and Treatment, Guizhou Medical University, Guiyang, Guizhou, China.

Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, China.

出版信息

Cancer Biol Ther. 2023 Dec 31;24(1):2249170. doi: 10.1080/15384047.2023.2249170.

DOI:10.1080/15384047.2023.2249170
PMID:37647260
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10469431/
Abstract

Sinapine thiocyanate (ST), an alkaloid existed extensively in seeds of cruciferous plants, exhibits a number of pharmacological effects, including anti-inflammatory and anti-malignancy properties. However, it is still unknown what effects and molecular mechanisms ST has on colorectal cancer (CRC). In the current study, it was indicated that ST inhibited proliferation, colony formation, and apoptosis , as well as arrested the G1 phase of CRC cells. There was a significant repressive effects of ST on invasion and migration of CRC cells . RNA-sequencing indicated that 750 differentially expressed genes existed in CRC cells after ST treatment, and enrichment analysis demonstrated that ST obviously decreased the activation of keratinization pathways. Among DEGs enriched in keratinization, keratin 6A (KRT6A) was decreased the most significant, as well as its target gene S100 calcium-binding protein A2 (S100A2). Low expression of KRT6A and S100A2 signatures indicated a favorable prognosis in CRC patients. Moreover, we found overexpression of KRT6A relieved the inhibitory effects of ST in CRC cells. Furthermore, ST inhibited the CRC cell proliferation , and reduced KRT6A and KI67 expression in xenograft tumor. Taken together, we demonstrated that ST exhibited anti-CRC properties by inhibiting KRT6A/S100A2 axis. It is possible that ST can be used as a treatment for CRC.

摘要

芥子氰酸硫苷（ST）是十字花科植物种子中广泛存在的一种生物碱，具有多种药理作用，包括抗炎和抗癌特性。然而，ST 对结直肠癌（CRC）的作用和分子机制尚不清楚。在本研究中，表明 ST 抑制 CRC 细胞的增殖、集落形成和凋亡，并使细胞停滞在 G1 期。ST 对 CRC 细胞的侵袭和迁移有明显的抑制作用。RNA-seq 表明 ST 处理后 CRC 细胞中有 750 个差异表达基因，富集分析表明 ST 明显降低了角化途径的激活。在富含角化的 DEGs 中，角蛋白 6A（KRT6A）的下调最为显著，其靶基因 S100 钙结合蛋白 A2（S100A2）也是如此。KRT6A 和 S100A2 标志物的低表达表明 CRC 患者的预后良好。此外，我们发现 KRT6A 的过表达缓解了 ST 对 CRC 细胞的抑制作用。此外，ST 抑制 CRC 细胞增殖，并降低异种移植肿瘤中 KRT6A 和 KI67 的表达。综上所述，我们证明 ST 通过抑制 KRT6A/S100A2 轴发挥抗 CRC 作用。ST 可能可用于 CRC 的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/3af2da21e780/KCBT_A_2249170_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/0d2ac624af5e/KCBT_A_2249170_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/7519d636fe19/KCBT_A_2249170_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/ff5606193286/KCBT_A_2249170_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/356df681dab6/KCBT_A_2249170_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/0e8cc4caa06a/KCBT_A_2249170_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/da72c22fc278/KCBT_A_2249170_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/3af2da21e780/KCBT_A_2249170_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/0d2ac624af5e/KCBT_A_2249170_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/7519d636fe19/KCBT_A_2249170_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/ff5606193286/KCBT_A_2249170_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/356df681dab6/KCBT_A_2249170_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/0e8cc4caa06a/KCBT_A_2249170_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/da72c22fc278/KCBT_A_2249170_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e63/10469431/3af2da21e780/KCBT_A_2249170_F0007_OC.jpg

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