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Tectorigenin 通过调节长链非编码 RNA CCAT2/miR-145 通路抑制结直肠癌细胞糖酵解诱导的生长和增殖。

Tectorigenin Inhibits Glycolysis-induced Cell Growth and Proliferation by Modulating LncRNA CCAT2/miR-145 Pathway in Colorectal Cancer.

机构信息

Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

出版信息

Curr Cancer Drug Targets. 2024;24(10):1071-1079. doi: 10.2174/0115680096274757231219072003.


DOI:10.2174/0115680096274757231219072003
PMID:38243936
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11340290/
Abstract

BACKGROUND: Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin (Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies. However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported. OBJECTIVE: The objective of this study was to explore the action of Tec in proliferation and glycolysis in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA) CCAT2/micro RNA-145(miR-145) pathway and . METHODS: The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized to detect glucose consumption and lactate production in the supernatant of cells and animal serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime quantitative PCR (RT-qPCR). RESULTS: Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2 overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the expression of miR-145 increased after Tec treatment . CONCLUSION: Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance for CRC treatment and new drug development.

摘要

背景:结直肠癌(CRC)给全球健康带来了沉重负担。Tectorigenin(Tec)是一种从中国药用植物虎眼万年青根茎中提取的类黄酮化合物。先前的研究发现,它具有显著的抗肿瘤特性。然而,Tec 在结直肠癌中的作用及其分子机制尚未报道。

目的:本研究旨在探讨 Tec 在 CRC 细胞增殖和糖酵解中的作用及其潜在机制,涉及长链非编码 RNA(lncRNA)CCAT2/微小 RNA-145(miR-145)通路。

方法:在细胞和动物研究中,采用细胞计数试剂盒-8(CCK-8)测定法和异种移植模型实验,检测 Tec 在 CRC 中的抗肿瘤作用。应用试剂盒检测细胞上清液和动物血清中的葡萄糖消耗和乳酸生成。通过 Western Blotting 检测糖酵解相关蛋白的表达,实时定量 PCR(RT-qPCR)检测 CRC 组织标本和细胞中 lncRNA CCAT2 和 miR-145 的水平。

结果: Tec 显著抑制 CRC 细胞的糖酵解和增殖率。它可以降低 CRC 细胞中的 lncRNA CCAT2,但增加 miR-145 的表达。lncRNA CCAT2 过表达或抑制 miR-145 可消除 Tec 对 CRC 细胞增殖和糖酵解的抑制作用。miR-145 模拟物可挽救 lncRNA CCAT2 过表达引起的细胞活力和糖酵解水平的增加。 Tec 显著抑制 CRC 异种移植肿瘤的生长和糖酵解。 Tec 治疗后,lncRNA CCAT2 的表达降低,而 miR-145 的表达增加。

结论: Tec 可通过 lncRNA CCAT2/miR-145 轴抑制 CRC 细胞的增殖和糖酵解。总之,本研究发现的潜在靶点对 CRC 的治疗和新药开发具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/9a1ab9460a5f/CCDT-24-1071_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/4eabf20e2442/CCDT-24-1071_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/8f58091b0473/CCDT-24-1071_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/a348043154d9/CCDT-24-1071_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/9a1ab9460a5f/CCDT-24-1071_F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/4eabf20e2442/CCDT-24-1071_F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/8f58091b0473/CCDT-24-1071_F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/a348043154d9/CCDT-24-1071_F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870a/11340290/9a1ab9460a5f/CCDT-24-1071_F4.jpg

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引用本文的文献

[1]
Glucose Metabolic Reprogramming in Colorectal Cancer: From Mechanisms to Targeted Therapy Approaches.

Cancer Med. 2025-9

[2]
CCAT2 role in gastrointestinal cancer progression and metastasis: a novel target for therapeutic strategies.

Clin Exp Med. 2025-6-11

本文引用的文献

[1]
Sprayed Nanovaccine Suppressing Exosomal PD-L1 by Golgi Apparatus Disorganization for Postsurgical Melanoma Immunotherapy.

ACS Nano. 2023-6-13

[2]
CCAT2 knockdown inhibits cell growth, and migration and promotes apoptosis through regulating the hsa-mir-145-5p/AKT3/mTOR axis in tamoxifen-resistant MCF7 cells.

Life Sci. 2022-12-15

[3]
Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications.

J Hematol Oncol. 2022-11-1

[4]
Effect of long noncoding RNA CCAT2 on drug sensitivity to 5-fluorouracil of breast cancer cells through microRNA-145 meditated by p53.

J Biochem Mol Toxicol. 2022-11

[5]
Glycolysis-Related LINC02432/Hsa-miR-98-5p/HK2 Axis Inhibits Ferroptosis and Predicts Immune Infiltration, Tumor Mutation Burden, and Drug Sensitivity in Pancreatic Adenocarcinoma.

Front Pharmacol. 2022-6-20

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Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells.

Life (Basel). 2022-5-30

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CA Cancer J Clin. 2022-9

[8]
Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway.

Bioengineered. 2022-5

[9]
NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer.

J Exp Clin Cancer Res. 2022-6-11

[10]
lncRNA-LET Regulates Glycolysis and Glutamine Decomposition of Esophageal Squamous Cell Carcinoma Through miR-93-5p/miR-106b-5p/SOCS4.

Front Oncol. 2022-5-10

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