Crucial Roles of LncRNAs-Mediated Autophagy in Breast Cancer

Han, Xing; Mo, Jinggang; Yang, Yingmei; Wang, Yichao; Lu, Hongsheng

doi:10.7150/ijms.72621

Cited by 12 publications

(6 citation statements)

References 90 publications

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“…The main purpose of this study was to use CRISPR/Cas9 technology to explore the role of a potential enhancer, referred to as Her2-Enhancer1, in the HER2 sequence as a regulatory element affecting the transcriptional balance of HER2 variants and other genes, such as the tumor suppressor GAS5 (growth arrest-specific 5) and the AKT/mTOR pathway. Growth arrest-specific 5 ability to inhibit tumor proliferation and induce apoptosis shows promising therapeutic potential (2,16). Grossi et al (as cited in Li et al) identified that GAS5 is downregulated in trastuzumabresistant HER2-positive BC cells (1).…”

Section: Discussionmentioning

confidence: 99%

Gene Editing for Unraveling the Regulatory Role of a HER2-Associated Enhancer with lncRNA GAS5 and Related Genes in Breast Cancer Cells

Rojhannezhad,

Mowla,

Rojhannezhad

et al. 2024

J Adv Immunopharmacol

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Background: The HER2/neu gene belongs to the epidermal growth factor receptor (EGFR) family and encodes a 185 kDa protein with tyrosine kinase activity. HER2 amplification or overexpression has been associated with tumorigenesis and cancer progression, notably in breast cancer (BC). The long non-coding RNA GAS5 has been recognized as a tumor suppressor in BC, promoting apoptosis and inhibiting cell proliferation. Moreover, GAS5 regulates key signaling pathways in breast cancer, including PI3K/AKT/mTOR and PTEN signaling. The PI3K/AKT pathway is critical in various cancer processes, such as proliferation, apoptosis, invasion, and drug resistance. Breast cancer stem cells (BCSCs) and stemness genes also contribute to tumor growth and therapy resistance. Therefore, targeting key regulatory regions in the HER2 gene could offer potential therapeutic strategies. Objectives: In this study, we aimed to investigate the regulatory role of a putative enhancer located in the HER2 gene in the 17q12 region (GH17J039694; we referred to it as Her2-Enhancer1 in our previous study) on HER2 variants and genes that are connected to it through different pathways. Methods: We analyzed the effects of enhancer knockout on HER2 variants, GAS5, PTEN, and stemness genes in HER2-positive and HER2-negative breast cancer cells using the CRISPR/Cas9 system and real-time PCR. Results: Our results showed significantly reduced HER2 variant expression in both cell lines after genetic editing. Furthermore, the expression of some other target genes was affected, including GAS5, P53, and PTEN. Interestingly, we observed altered expression of stemness genes like NANOG, SOX2, and OCT4, indicating possible implications for cancer stem cell properties. Conclusions: Our study highlights the potential regulatory role of the studied region as an enhancer in the HER2 gene and sheds light on its influence on various cancer-related pathways, providing valuable insights into breast cancer pathogenesis and potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Gene Editing for Unraveling the Regulatory Role of a HER2-Associated Enhancer with lncRNA GAS5 and Related Genes in Breast Cancer Cells

Rojhannezhad,

Mowla,

Rojhannezhad

et al. 2024

J Adv Immunopharmacol

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“…Autophagy is initiated under a variety of stress conditions (e.g., starvation, hypoxia and oxidative stress) by the release of signals that lead to the activation of the ULK1 complex, which consists of the central kinase protein ULK1, ATG13, FIP200 and ATG101 ( Klionsky et al, 2021 ; C. W; Yun and Lee, 2018 ). AMPK and mTORC1 regulate autophagy induction ( Ktistakis and Tooze, 2016 ; Han et al, 2022 ). Under nutrient-rich conditions, mTORC1 is a repressor of autophagy, which can bind ULK1 and avoid autophagy initiation.…”

Section: Overview Of Lncrnamentioning

confidence: 99%

The role of LncRNA-mediated autophagy in cancer progression

Liu,

Tang,

Yang

et al. 2024

Front. Cell Dev. Biol.

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Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

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“…ATG10 is activated by direct binding of the lncRNA AGAP2-AS1–ELAVL1 complex to its promoter region [ 21 ]. LncRNAs, including HOTAIR, TALNEC2, EGOT, ZNF649, GAS5, DANCR, OTUD6B, and NAMPT, have been reported to regulate the expression of autophagy-associated proteins and impact cancer progression [ 22 , 23 ].…”

Section: Autophagy a Complex Process Designed To Support Cell Death A...mentioning

confidence: 99%

Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

Sharma

2023

Cells

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Despite an increase in the incidence of breast cancer worldwide, overall prognosis has been consistently improving owing to the development of multiple targeted therapies and novel combination regimens including endocrine therapies, aromatase inhibitors, Her2-targeted therapies, and cdk4/6 inhibitors. Immunotherapy is also being actively examined for some breast cancer subtypes. This overall positive outlook is marred by the development of resistance or reduced efficacy of the drug combinations, but the underlying mechanisms are somewhat unclear. It is interesting to note that cancer cells quickly adapt and evade most therapies by activating autophagy, a catabolic process designed to recycle damaged cellular components and provide energy. In this review, we discuss the role of autophagy and autophagy-associated proteins in breast cancer growth, drug sensitivity, tumor dormancy, stemness, and recurrence. We further explore how autophagy intersects and reduces the efficacy of endocrine therapies, targeted therapies, radiotherapy, chemotherapies as well as immunotherapy via modulating various intermediate proteins, miRs, and lncRNAs. Lastly, the potential application of autophagy inhibitors and bioactive molecules to improve the anticancer effects of drugs by circumventing the cytoprotective autophagy is discussed.

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Crucial Roles of LncRNAs-Mediated Autophagy in Breast Cancer

Cited by 12 publications

References 90 publications

Gene Editing for Unraveling the Regulatory Role of a HER2-Associated Enhancer with lncRNA GAS5 and Related Genes in Breast Cancer Cells

Gene Editing for Unraveling the Regulatory Role of a HER2-Associated Enhancer with lncRNA GAS5 and Related Genes in Breast Cancer Cells

The role of LncRNA-mediated autophagy in cancer progression

Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

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