MiR-7 mediates mitochondrial impairment to trigger apoptosis and necroptosis in Rhabdomyosarcoma

Yang, Lin; Kong, Delin; He, Mei; Gong, Jiawei; Nie, Yuzhe; Tai, Sheng; Teng, Chun‐Bo

doi:10.1016/j.bbamcr.2020.118826

Cited by 21 publications

(14 citation statements)

References 48 publications

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“…21,22 MiR-7-5p mediates mitochondrial damage by targeting mitochondrial proteins SLC25A37 and TIMM50, thereby inducing apoptosis and necroptosis of rhabdomyosarcoma cells. 23 Recently, lncRNA TINCR could serve as a miR-7-5p sponge was proposed to be associated with colorectal cancer progression, which may promote the development of colorectal cancer mediated by miR-7-5p. 24 MiR-223-3p negatively manages the expression of RIP3, and it significantly affects the inhibition of RIP3-mediated necroptosis and inflammation to reduce spinal cord neuron damage.…”

Section: Discussionmentioning

confidence: 99%

A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer

Yang¹,

Lü²,

Wang³

et al. 2022

IJGM

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This study aims at exploring the relationship between necroptosis-related miRNAs and colon cancer prognosis. Methods: We downloaded the miRNA sequencing data from the TCGA, and eight differentially expressed necroptosis-related miRNAs were screened. Then, we used Cox regression analysis to establish a prediction model of necroptosis-related miRNA. Finally, the prognosis related miRNAs were used to predict the target genes, and functional analysis was used to explore the potential mechanism of these target genes. Results:The miRNA-seq data of 444 COAD cases were downloaded from TCGA. We identified 8 differentially expressed miRNAs (has-miR-16-5p, has-miR-141-3p, has-miR -148a-3p, has-miR-425-5p, has-miR-7-5p, has-miR-223-3p, has-miR-200a-5p, and has-miR -500a-3p), then Cox analysis was performed for determining eight-miRNA signature prognostic biomarkers with obviously different OS. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for predicting 1-, 3-, and 5-year survival were 0.663, 0.653 and 0.639, respectively. The multivariate analysis also implied that the risk score was an independent prognostic factor considering other confounding factors (HR = 1.847, 95% CI = 1.197-2.848, P = 0.006). According to the Kaplan-Meier analysis, the expression of hsa-miR-500a-3p (P = 0.003), hsa-miR-16-5p (P = 0.004) and hsa-miR-148a-3p (P = 0.035) significantly affected OS outcomes. We predicted the target genes of these three miRNAs and then screened 10 hub genes (CCND1, SMAD3, SMAD2, CDK1, TGFB2, CDC25A, CHEK1, VEGFA, CCNE1, WEE1). In addition, CHEK1 was associated with the survival prognosis. Conclusion: Our study demonstrated that necroptosis is closely associated with colon cancer, and the model of eight necroptosis-related miRNAs are potentially useful prognostic biomarkers and therapeutic targets for colon cancer.

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Section: Discussionmentioning

confidence: 99%

A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer

Yang¹,

Lü²,

Wang³

et al. 2022

IJGM

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“…miR-148a served as the tumor suppressor gene to inhibit cancer metastasis [ 140 – 142 ]. miRNAs miR-7-5p SLC25A37 cTIMM50 NOVA2 HOXB13 miR-7 is reported to induce necroptosis by targeting SLC25A37 and TIMM50 to work as a tumor-suppressive gene [ 32 ]. MiR-7-5p was reported to inhibit tumor metastasis by targeting NOVA2 in NSCLC cancers [ 29 ], RELA in breast cancer stem cells [ 30 ], and HOXB13 in esophageal squamous cell carcinoma [ 31 ].…”

Section: Necroptosis and Cancer Metastasismentioning

confidence: 99%

“…MiR-7-5p was reported to inhibit tumor metastasis by targeting NOVA2 in NSCLC cancers [ 29 ], RELA in breast cancer stem cells [ 30 ] and HOXB13 in esophageal squamous cell carcinoma [ 31 ]. In rhabdomyosarcoma (RMS), miR-7 showed the anti-tumor effect to induce necroptosis by targeting mitochondrial proteins SLC25A37 and TIMM50 [ 32 ]. SLC25A37 was significantly over-expressed in high cytotoxicity patients [ 33 ] and loss of TIM50 suppressed tumor cell growth and induced apoptosis in breast cancer [ 34 ] and loss of TIM50 suppressed tumor cell growth and induced apoptosis in breast cancer [ 35 ].…”

Section: Necroptosis and Cancer Metastasismentioning

confidence: 99%

Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis

et al. 2021

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Distant metastasis is the main cause of death for cancer patients. Recently, the newly discovered programmed cell death includes necroptosis, pyroptosis, and ferroptosis, which possesses an important role in the process of tumor metastasis. At the same time, it is widely reported that non-coding RNA precisely regulates programmed death and tumor metastasis. In the present review, we summarize the function and role of necroptosis, pyrolysis, and ferroptosis involving in cancer metastasis, as well as the regulatory factors, including non-coding RNAs, of necroptosis, pyroptosis, and ferroptosis in the process of tumor metastasis.

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“…Subsequently, the miR-7-5p gain-of-function assay identified its cancer-inhibitory effect on AML cells. It has been shown that miR-7-5p is pivotal for the inhibition of cancer progression and to suppress the proliferative, migratory, and invasive activities of a variety of oncocytes by targeting different genes [ 42 ]. In addition, miR-7-5p can increase the sensitivity of breast carcinoma cells to adriamycin after inhibiting the epidermal growth factor (EGF) receptor/PI3K signaling pathway [ 43 ], and can inhibit the proliferation and metastasis of osteosarcoma cells by targeting insulin-like growth factor 1 receptor [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11

Jiang

Sun

et al. 2022

J Nanobiotechnol

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Background Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation of abnormal blasts and leukemia cells in the bone marrow and the inhibition of normal hematopoiesis at onset. Exosomes containing proteins or nucleic acids are secreted by cells; they participate in intercellular communication and serve as key modulators of hematopoiesis. The purpose of this study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the regulation of AML and the underlying mechanisms mediated by microRNA (miRNA). Methods Dysregulated miR-7-5p in AML patients was identified using qRT-PCR and its clinical significance was explored. Bioinformatic analysis revealed the target gene OSBPL11 that could be regulated by miR-7-5p. The findings were validated using a dual-luciferase reporter assay and western blotting. The functional genes of the PI3K/AKT/mTOR signaling pathway were identified, and the functional significance of miR-7-5p in AML cells was determined using a functional recovery assay. AML cells were co-cultured with exosomes originating from BMSCs overexpressing miR-7-5p to determine cell–cell regulation by Exo-miR-7-5p, as well as in vitro and in vivo functional validation via gain- and loss-of-function methods. Results Expression of miR-7-5p was decreased in AML patients and cells. Overexpression of miR-7-5p curbed cellular proliferation and promoted apoptosis. Overexpression of OSBPL11 reversed the tumorigenic properties of miR-7-5p in AML cells in vitro. Exo-miR-7-5p derived from BMSCs induced formation of AML cells prone to apoptosis and a low survival rate, with OSBPL11 expression inhibited through the PI3K/AKT/mTOR signaling pathway. Exo-miR-7-5p derived from BMSCs exhibited tumor homing effects in vitro and in vivo, and inhibited AML development. Conclusions Exo-miR-7-5p derived from BMSCs negatively regulates OSBPL11 by suppressing the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting AML proliferation and promoting apoptosis. The data will inform the development of AML therapies based on BMSC-derived exosomes. Graphical Abstract

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MiR-7 mediates mitochondrial impairment to trigger apoptosis and necroptosis in Rhabdomyosarcoma

Cited by 21 publications

References 48 publications

A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer

A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer

Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis

Bone mesenchymal stem cell-derived exosomal microRNA-7-5p inhibits progression of acute myeloid leukemia by targeting OSBPL11

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