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姜黄素通过调控 circ-PLEKHM3/miR-320a/SMG1 轴抑制卵巢癌细胞进展。

Curcumin inhibits ovarian cancer progression by regulating circ-PLEKHM3/miR-320a/SMG1 axis.

机构信息

Department of Rehabilitation, The Second Hospital of Dalian Medical University, Dalian City, Liaoning Province, China.

Department of Traditional Chinese Medicine, The Second Hospital of Dalian Medical University, No.467 Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China.

出版信息

J Ovarian Res. 2021 Nov 16;14(1):158. doi: 10.1186/s13048-021-00916-8.

DOI:10.1186/s13048-021-00916-8
PMID:34784955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8594156/
Abstract

BACKGROUND: Curcumin has a potential therapeutic role in ovarian cancer. However, whether curcumin plays anti-cancer role in ovarian cancer by mediating the circular RNA (circRNA)/microRNA (miRNA)/mRNA network is still unclear. METHODS: The expression of circ-PLEKHM3, miR-320a, and suppressor of morphogenesis in genitalia 1 (SMG1) was detected via qRT-PCR. Cell viability, colony-formation ability and apoptosis were analyzed via cell counting kit-8 assay, colony formation analysis, and flow cytometry. Protein expression was measured using western blot. The in vivo experiments were performed using a xenograft model. Target association was evaluated via dual-luciferase reporter analysis and RIP assay. RESULTS: Curcumin suppressed ovarian cancer cell proliferation and promoted apoptosis. Circ-PLEKHM3 was downregulated in ovarian cancer, and its expression could be promoted by curcumin treatment. Circ-PLEKHM3 overexpression exacerbated the effect of curcumin on ovarian cancer cell proliferation and apoptosis, as well as anti-tumor effect. MiR-320a was targeted by circ-PLEKHM3. The inhibition effect of circ-PLEKHM3 overexpression on cell proliferation and the enhancing effect on cell apoptosis could be reversed by miR-320a mimic. SMG1 was targeted by miR-320a, and its knockdown also reversed the regulation of miR-320a inhibitor on the proliferation and apoptosis of ovarian cancer cells. In addition, circ-PLEKHM3 could upregulate SMG1 expression via sponging miR-320a. CONCLUSION: Curcumin restrained proliferation and facilitated apoptosis in ovarian cancer by regulating the circ-PLEKHM3/miR-320a/SMG1 axis.

摘要

背景：姜黄素在卵巢癌中具有潜在的治疗作用。然而，姜黄素是否通过调节环状 RNA（circRNA）/微小 RNA（miRNA）/mRNA 网络发挥抗癌作用尚不清楚。

方法：通过 qRT-PCR 检测 circ-PLEKHM3、miR-320a 和生殖器形态发生抑制因子 1（SMG1）的表达。通过细胞计数试剂盒-8 测定、集落形成分析和流式细胞术分析细胞活力、集落形成能力和细胞凋亡。使用 Western blot 测定蛋白表达。使用异种移植模型进行体内实验。通过双荧光素酶报告分析和 RIP 测定评估靶标关联。

结果：姜黄素抑制卵巢癌细胞增殖并促进凋亡。circ-PLEKHM3 在卵巢癌中下调，其表达可被姜黄素处理所促进。circ-PLEKHM3 过表达加剧了姜黄素对卵巢癌细胞增殖和凋亡的影响，以及对肿瘤的抑制作用。circ-PLEKHM3 靶向 miR-320a。circ-PLEKHM3 过表达对细胞增殖的抑制作用和对细胞凋亡的增强作用可被 miR-320a 模拟物逆转。SMG1 是 miR-320a 的靶标，SMG1 敲低也可逆转 miR-320a 抑制剂对卵巢癌细胞增殖和凋亡的调节作用。此外，circ-PLEKHM3 通过海绵吸附 miR-320a 来上调 SMG1 表达。

结论：姜黄素通过调节 circ-PLEKHM3/miR-320a/SMG1 轴抑制卵巢癌细胞增殖并促进凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/2f61bb99d16a/13048_2021_916_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/4ae67a093b0d/13048_2021_916_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/69beb9f6231a/13048_2021_916_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/ef35c4fc3c45/13048_2021_916_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/850f6cb65638/13048_2021_916_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/fdf174b1a196/13048_2021_916_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/919fbb6f16a9/13048_2021_916_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/e6a3c43fd09e/13048_2021_916_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/2f61bb99d16a/13048_2021_916_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/4ae67a093b0d/13048_2021_916_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/69beb9f6231a/13048_2021_916_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/ef35c4fc3c45/13048_2021_916_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/850f6cb65638/13048_2021_916_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/fdf174b1a196/13048_2021_916_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/919fbb6f16a9/13048_2021_916_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/e6a3c43fd09e/13048_2021_916_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fba6/8594156/2f61bb99d16a/13048_2021_916_Fig8_HTML.jpg

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引用本文的文献

[1]
Long Non-Coding, Micro, and Circular RNAs in Ovarian Cancer Metastasis: Pathways and Treatment Approaches.

Reprod Sci. 2025-8-15

[2]
Natural Antioxidants as Regulators of Circular RNA Expression and Function.

Wiley Interdiscip Rev RNA. 2025

[3]
Curcumin induces mitochondrial dysfunction-associated oxidative DNA damage in ovarian cancer cells.

PLoS One. 2025-3-31

[4]
Mechanism of Curcumin in the Treatment of Intrauterine Adhesions Based on Network Pharmacology, Molecular docking, and Experimental Validation.

Biochem Genet. 2025-2-13

[5]
Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.

Cancers (Basel). 2024-12-16

[6]
Effect of icariin on ovarian cancer: a combined network pharmacology and meta-analysis of studies approach.

Front Pharmacol. 2024-12-20

[7]
Development of the Curcumin Analog CA7 Liposome and Its Evaluation for Efficacy Against Cervical Cancer in vitro and in vivo.

Int J Nanomedicine. 2024-12-13

[8]
Therapeutic Potential of Natural Compounds to Modulate WNT/β-Catenin Signaling in Cancer: Current State of Art and Challenges.

Int J Mol Sci. 2024-11-28

[9]
Circ_0001741 exerts as a tumor promoter in ovarian cancer through the regulation of miR-491-5p/PRSS8 axis.

Discov Oncol. 2024-11-11

[10]
A nanoscale natural drug delivery system for targeted drug delivery against ovarian cancer: action mechanism, application enlightenment and future potential.

Front Immunol. 2024

本文引用的文献

[1]
MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8.

Front Oncol. 2021-2-25

[2]
Curcumin suppresses the malignancy of non-small cell lung cancer by modulating the circ-PRKCA/miR-384/ITGB1 pathway.

Biomed Pharmacother. 2021-6

[3]
Withdrawn: Z. Cui, Q. Sun, W. Yan, Q. Han, G. Wang, Y. Hu. The role of miR-320a and its target gene GMEB1 in epithelial-mesenchymal transition and invasion of colorectal cancer, published in The Journal of Gene Medicine.

J Gene Med. 2023-4

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Long Non-Coding RNA GAS5 Suppresses Tumor Progression and Enhances the Radiosensitivity of Prostate Cancer Through the miR-320a/RAB21 Axis.

Cancer Manag Res. 2020-9-22

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Downregulation of microRNA-320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3.

Exp Ther Med. 2020-11

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MicroRNA-32 promotes ovarian cancer cell proliferation and motility by targeting SMG1.

Oncol Lett. 2020-7

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Circular RNA hsa_circ_0078607 suppresses ovarian cancer progression by regulating miR-518a-5p/Fas signaling pathway.

J Ovarian Res. 2020-6-5

[8]
Curcumin Enhances Radiosensitization of Nasopharyngeal Carcinoma via Mediating Regulation of Tumor Stem-like Cells by a CircRNA Network.

J Cancer. 2020-2-10

[9]
miRNA profile in ovarian cancer.

Exp Mol Pathol. 2020-1-16

[10]
Curcumin enhances radiosensitization of nasopharyngeal carcinoma by regulating circRNA network.

Mol Carcinog. 2019-12-2

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