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miRNA 变异对三阴性乳腺癌中 PI3K/AKT 信号的影响:全面综述。

Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.

机构信息

Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Med Oncol. 2024 Aug 9;41(9):222. doi: 10.1007/s12032-024-02469-4.


DOI:10.1007/s12032-024-02469-4
PMID:39120634
Abstract

Breast cancer (BC) is a significant cause of cancer-related mortality, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype associated with high mortality rates, especially among younger females. TNBC poses a considerable clinical challenge due to its aggressive tumor behavior and limited therapeutic options. Aberrations within the PI3K/AKT pathway are prevalent in TNBC and correlate with increased therapeutic intervention resistance and poor outcomes. MicroRNAs (miRs) have emerged as crucial PI3K/AKT pathway regulators influencing various cellular processes involved in TNBC pathogenesis. The levels of miRs, including miR-193, miR-4649-5p, and miR-449a, undergo notable changes in TNBC tumor tissues, emphasizing their significance in cancer biology. This review explored the intricate interplay between miR variants and PI3K/AKT signaling in TNBC. The review focused on the molecular mechanisms underlying miR-mediated dysregulation of this pathway and highlighted specific miRs and their targets. In addition, we explore the clinical implications of miR dysregulation in TNBC, particularly its correlation with TNBC prognosis and therapeutic resistance. Elucidating the roles of miRs in modulating the PI3K/AKT signaling pathway will enhance our understanding of TNBC biology and unveil potential therapeutic targets. This comprehensive review aims to discuss current knowledge and open promising avenues for future research, ultimately facilitating the development of precise and effective treatments for patients with TNBC.

摘要

乳腺癌(BC)是癌症相关死亡率的重要原因,三阴性乳腺癌(TNBC)是一种特别具有侵袭性的亚型,与高死亡率相关,尤其是在年轻女性中。TNBC 由于其侵袭性肿瘤行为和有限的治疗选择,构成了相当大的临床挑战。PI3K/AKT 通路中的异常在 TNBC 中很常见,并与增加的治疗干预耐药性和不良预后相关。MicroRNAs(miRs)已成为 PI3K/AKT 通路的重要调节因子,影响参与 TNBC 发病机制的各种细胞过程。miRs 的水平,包括 miR-193、miR-4649-5p 和 miR-449a,在 TNBC 肿瘤组织中发生显著变化,强调了它们在癌症生物学中的重要性。本综述探讨了 miR 变体与 TNBC 中 PI3K/AKT 信号之间的复杂相互作用。综述重点介绍了 miR 介导的该通路失调的分子机制,并强调了特定的 miRs 及其靶标。此外,我们还探讨了 miR 失调在 TNBC 中的临床意义,特别是其与 TNBC 预后和治疗耐药性的相关性。阐明 miRs 在调节 PI3K/AKT 信号通路中的作用将增强我们对 TNBC 生物学的理解,并揭示潜在的治疗靶点。本综述旨在讨论当前的知识,并为未来的研究开辟有前途的途径,最终为 TNBC 患者的精确和有效治疗的发展提供帮助。

相似文献

[1]
Impact of microRNA variants on PI3K/AKT signaling in triple-negative breast cancer: comprehensive review.

Med Oncol. 2024-8-9

[2]
Hsa_circ_0000199 facilitates chemo-tolerance of triple-negative breast cancer by interfering with miR-206/613-led PI3K/Akt/mTOR signaling.

Aging (Albany NY). 2021-1-20

[3]
MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib.

Breast Cancer Res. 2023-10-6

[4]
Overexpression of miR-361-5p in triple-negative breast cancer (TNBC) inhibits migration and invasion by targeting RQCD1 and inhibiting the EGFR/PI3K/Akt pathway.

Bosn J Basic Med Sci. 2019-2-12

[5]
Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway.

Kaohsiung J Med Sci. 2020-8

[6]
WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer.

Cell Physiol Biochem. 2018

[7]
Long noncoding RNA GAS5 suppresses triple negative breast cancer progression through inhibition of proliferation and invasion by competitively binding miR-196a-5p.

Biomed Pharmacother. 2018-5-25

[8]
MiR-193 promotes cell proliferation and invasion by ING5/PI3K/AKT pathway of triple-negative breast cancer.

Eur Rev Med Pharmacol Sci. 2020-3

[9]
CircWAC induces chemotherapeutic resistance in triple-negative breast cancer by targeting miR-142, upregulating WWP1 and activating the PI3K/AKT pathway.

Mol Cancer. 2021-3-1

[10]
CircWHSC1 regulates malignancy and glycolysis by the miR-212-5p/AKT3 pathway in triple-negative breast cancer.

Exp Mol Pathol. 2021-12

引用本文的文献

[1]
The roles of non-coding RNAs (ncRNAs) in the function of leukemic stem cells (LSCs): a comprehensive review.

Discov Oncol. 2025-8-25

[2]
The Effect and Treatment of PIK3CA Mutations in Breast Cancer: Current Understanding and Future Directions.

Medicina (Kaunas). 2025-3-17

[3]
Clinical research on triple-negative breast cancer that targets the PIK3CA pathway.

Med Oncol. 2024-10-14

本文引用的文献

[1]
Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

JOR Spine. 2024-1-2

[2]
Detailed role of microRNA-mediated regulation of PI3K/AKT axis in human tumors.

Cell Biochem Funct. 2024-1

[3]
MicroRNA‑606 inhibits the growth and metastasis of triple‑negative breast cancer by targeting Stanniocalcin 1.

Oncol Rep. 2024-1

[4]
MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib.

Breast Cancer Res. 2023-10-6

[5]
Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR.

J Transl Med. 2023-9-5

[6]
Recent advances in targeted strategies for triple-negative breast cancer.

J Hematol Oncol. 2023-8-28

[7]
miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer.

Genes (Basel). 2023-6-29

[8]
Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.

Front Oncol. 2023-6-19

[9]
The impact of lipid metabolism on breast cancer: a review about its role in tumorigenesis and immune escape.

Cell Commun Signal. 2023-6-27

[10]
FSTL1 Suppresses Triple-Negative Breast Cancer Lung Metastasis by Inhibiting M2-like Tumor-Associated Macrophage Recruitment toward the Lungs.

Diagnostics (Basel). 2023-5-12

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