SLC7A11/ xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells

Yadav, Poonam; Sharma, Priyanshu; Sundaram, Sandhya; Venkatraman, Ganesh; Bera, Amal Kanti; Karunagaran, Devarajan

doi:10.1016/j.canlet.2021.09.033

Cited by 78 publications

(47 citation statements)

References 73 publications

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“…One of the predicted binding sites for the hsa-miR-5096 is the CRE site at the HLA-G promoter, which induces gene transcription in response to cAMP ( Gobin et al, 2002 ). The hsa-miR-5096 was reported as a potential tumor suppressor miRNA capable of inhibiting the proliferation, migration, and invasion of breast cancer cells in vitro by targeting the SLC7A11 gene, which is related to ferroptosis resistance ( Yadav et al, 2021 ). On the other hand, Thuringer et al (2017) demonstrated an oncogene role for hsa-miR-5096 whose high expression contributed to increased invasiveness of glioblastoma cells by decreasing Kir4.1 protein levels, a K+ channel involved in the ionic homeostasis in the brain ( Thuringer et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia

et al. 2022

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HLA-G is a nonclassical histocompatibility class I molecule that plays a role in immune vigilance in cancer and infectious diseases. We previously reported that highly soluble HLA-G (sHLA-G) levels in the bone marrow were associated with a high blood cell count in T-acute lymphoblastic leukemia, a marker associated with a poor prognosis. To understand the posttranscriptional HLA-G gene regulation in leukemia, we evaluated the bone marrow microRNA profile associated with the HLA-G bone marrow mRNA expression and sHLA-G bone marrow levels in children exhibiting acute leukemia (B-ALL, T-ALL, and AML) using massively parallel sequencing. Ten differentially expressed miRNAs were associated with high sHLA-G bone marrow levels, and four of them (hsa-miR-4516, hsa-miR-486-5p, hsa-miR-4488, and hsa-miR-5096) targeted HLA-G, acting at distinct HLA-G gene segments. For qPCR validation, these miRNA expression levels (ΔCt) were correlated with HLA-G5 and RREB1 mRNA expressions and sHLA-G bone marrow levels according to the leukemia subtype. The hsa-miR-4488 and hsa-miR-5096 expression levels were lower in B-ALL than in AML, while that of hsa-miR-486-5p was lower in T-ALL than in AML. In T-ALL, hsa-miR-5096 correlated positively with HLA-G5 and negatively with sHLA-G. In addition, hsa-miR-4516 correlated negatively with sHLA-G levels. In AML, hsa-miR-4516 and hsa-miR-4488 correlated positively with HLA-G5 mRNA, but the HLA-G5 negatively correlated with sHLA-G. Our findings highlight the need to validate the findings of massively parallel sequencing since the experiment generally uses few individuals, and the same type of leukemia can be molecularly quite variable. We showed that miRNA’s milieu in leukemia’s bone marrow environment varies according to the type of leukemia and that the regulation of sHLA-G expression exerted by the same miRNA may act by a distinct mechanism in different types of leukemia.

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Section: Discussionmentioning

confidence: 99%

Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia

et al. 2022

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“…The restoration of xCT inhibits miR-5096–induced ferroptosis and anticancer effects on human breast carcinoma cells by mediating lipid ROS, iron accumulation and GSH levels. A preclinical trial reported that miR-5096 contributes to inhibiting the colony formation, invasion and migration of cancer cells, while anti-miR-5096 significantly stimulates these carcinogenic features ( Yadav et al, 2021 ). At present, the interaction among miRNAs, ferroptosis and cancer metastasis has not been fully elucidated, which requires further in-depth research.…”

Section: Ferroptosis and Cancer Metastasismentioning

confidence: 99%

Targeting Ferroptosis Pathway to Combat Therapy Resistance and Metastasis of Cancer

Zhang

et al. 2022

Front. Pharmacol.

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Ferroptosis is an iron-dependent regulated form of cell death caused by excessive lipid peroxidation. This form of cell death differed from known forms of cell death in morphological and biochemical features such as apoptosis, necrosis, and autophagy. Cancer cells require higher levels of iron to survive, which makes them highly susceptible to ferroptosis. Therefore, it was found to be closely related to the progression, treatment response, and metastasis of various cancer types. Numerous studies have found that the ferroptosis pathway is closely related to drug resistance and metastasis of cancer. Some cancer cells reduce their susceptibility to ferroptosis by downregulating the ferroptosis pathway, resulting in resistance to anticancer therapy. Induction of ferroptosis restores the sensitivity of drug-resistant cancer cells to standard treatments. Cancer cells that are resistant to conventional therapies or have a high propensity to metastasize might be particularly susceptible to ferroptosis. Some biological processes and cellular components, such as epithelial–mesenchymal transition (EMT) and noncoding RNAs, can influence cancer metastasis by regulating ferroptosis. Therefore, targeting ferroptosis may help suppress cancer metastasis. Those progresses revealed the importance of ferroptosis in cancer, In order to provide the detailed molecular mechanisms of ferroptosis in regulating therapy resistance and metastasis and strategies to overcome these barriers are not fully understood, we described the key molecular mechanisms of ferroptosis and its interaction with signaling pathways related to therapy resistance and metastasis. Furthermore, we summarized strategies for reversing resistance to targeted therapy, chemotherapy, radiotherapy, and immunotherapy and inhibiting cancer metastasis by modulating ferroptosis. Understanding the comprehensive regulatory mechanisms and signaling pathways of ferroptosis in cancer can provide new insights to enhance the efficacy of anticancer drugs, overcome drug resistance, and inhibit cancer metastasis.

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“…System

plays an important role in GPX4 relative pathway, whether the system

dysfunction could result in the pool of GSH and GPX4 shrinking ( 35 ), and then gives birth to intracellular PLOOH explode and ultimately induces ferroptosis ( 26 , 33 ). The monitors regulating system

are SLC7A11 ( 39 ), SLC3A2 ( 40 ), NRF2 ( 41 ) and so on ( 42 ). Stephanie demonstrated that SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma ( 43 ) Ju et al.…”

Section: Overview Of Ferroptosis and Potential Singling Pathway In Gl...mentioning

confidence: 99%

Ferroptosis in Glioma Immune Microenvironment: Opportunity and Challenge

Wang

Zhang

et al. 2022

Front. Oncol.

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Glioma is the most common intracranial malignant tumor in adults and the 5-year survival rate of glioma patients is extremely poor, even in patients who received Stupp treatment after diagnosis and this forces us to explore more efficient clinical strategies. At this time, immunotherapy shows great potential in a variety of tumor clinical treatments, however, its clinical effect in glioma is limited because of tumor immune privilege which was induced by the glioma immunosuppressive microenvironment, so remodeling the immunosuppressive microenvironment is a practical way to eliminate glioma immunotherapy resistance. Recently, increasing studies have confirmed that ferroptosis, a new form of cell death, plays an important role in tumor progression and immune microenvironment and the crosstalk between ferroptosis and tumor immune microenvironment attracts much attention. This work summarizes the progress studies of ferroptosis in the glioma immune microenvironment.

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SLC7A11/ xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells

Cited by 78 publications

References 73 publications

Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia

Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia

Targeting Ferroptosis Pathway to Combat Therapy Resistance and Metastasis of Cancer

Ferroptosis in Glioma Immune Microenvironment: Opportunity and Challenge

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