<i>MIR106A-5p</i> upregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma

Zhu, Qingwen; Zhang, Qicheng; Gu, Miao; Zhang, Kaiwen; Xia, Tian; Zhang, Siyu; Chen, Wenhui; Yin, Haimeng; Yao, Hui; Fan, Yue; Pan, Si Yuan; Xie, Haijing; Liu, Huiting; Cheng, Tianyi; Zhang, Panpan; Zhang, Ting; You, Bo; You, Yiwen

doi:10.1080/15548627.2020.1781368

Cited by 51 publications

(35 citation statements)

References 56 publications

(65 reference statements)

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“…The autophagy process can be spontaneous and in dynamic equilibrium, or it can be activated under different stimuli. In addition to cell maintenance, autophagy is also involved in many physiological and pathological conditions, such as aging, apoptosis and cancer [ 27 ]. The role of autophagy is complex and differs in different types of cancer.…”

Section: Discussionmentioning

confidence: 99%

The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1

Peng

Zheng

Liu

et al. 2022

Infect Agents Cancer

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Background Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharyngeal mucosa of the head and neck. The role of long non-coding RNA and RNA methylation in NPC has received increasing attention. Therefore, this study aims to investigate the mechanism of lncRNA ZFAS1 in NPC and its relationship with RNA methylation, providing evidence for targeted therapy of NPC. Methods Microarray arrays were used to screen the differentially expressed miRNAs in normal tissues and tumor tissues. QRT-PCR was used to quantify ZFAS1, miR-100-3p, ATG10, autophagy and epithelial-mesenchymal transition related genes. The interactive relationship between ZFAS1 and miR-100-3p was verified using dual-luciferase reporter gene assay and RIP assay. CCK-8, transwell and apoptosis were used to detect the occurrence of tumor cells after different treatments. The m6A modification test is used to verify the effect of METTL3 on ZFAS1. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo. Results ZFAS1 is upregulated in tumor tissues and NPC cells. N (6)-methyladenosine (m6A) is highly enriched in ZFAS1 and enhances its RNA stability. ZFAS1 is used as an oncogenic lncRNA, which can promote NPC cell proliferation, migration and tumor growth. In terms of mechanism, ZFAS1 up-regulates the expression of ATG10 by competitively adsorbing miR-100-3p and regulates the level of autophagy by inhibiting the PI3K/Akt signaling pathway to promote the proliferation and migration of NPC cells. Conclusion In short, our study verified the cancer-promoting effect of ZFAS1 in NPC and explained part of the reason for its upregulation. In addition, we confirmed that ZFAS1 can regulate the autophagy level of NPC cells through the PI3K/AKT pathway through miR-100-3p/ATG10 to affect tumor progression.

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Section: Discussionmentioning

confidence: 99%

The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1

Peng

Zheng

Liu

et al. 2022

Infect Agents Cancer

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“…Transfection was performed as described previously [25] using ATG5-shRNA plasmids from Shanghai Genechem (Shanghai, China). Tandem monomeric RFP-GFP-tagged LC3 (Shanghai Genechem, tfLC3) was used to determine autophagic flux, as described previously [24] . To measure mitochondrial content and mitochondrial morphology, cells were incubated with 200 nM MitoTracker green mitochondrial probe (Cell Signaling, MA, USA, #9074) for 30 min at 37°C, collected, and live-imaged immediately using a confocal microscope (Leica Microsystems, TCS SP-5).…”

Section: Transfection and Transductionmentioning

confidence: 99%

AMPK–mTOR–Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells

You

Xia

et al. 2022

Cancer Research

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Dormant cancer cells that survive anti-cancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases.Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In this study, we report the biological properties of PGCC, including mitochondrial alterations, and reveal that autophagy is a critical mechanism of PGCC induction.Moreover, pharmacological or genetic inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, which then produced low ATP levels and activated autophagy via the AMPK-mTOR pathway to promote PGCC formation. Analysis of the transcriptional and epigenetic landscape of PGCC revealed overexpression of RIPK1, and the scaffolding function of RIPK1 was required for AMPK-mTOR pathway-induced PGCC survival. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in NPC patients. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer. SignificanceResearch.

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“…Mitogen-activated protein kinase (MAPK) signaling cascades are critical signal pathways related to EMT, which promotes cancer cell progression and metastasis in CSCs [ 132 ]. miR-106A-5p facilitates a malignant phenotype by acting as an autophagic suppressor through targeting BTG anti-proliferation factor 3 ( BTG3 ) and activates autophagy-regulating MAPK signaling in NPC [ 133 ]. MYC target 1 ( MYCT1 ), a direct target gene of MYC, is a novel candidate tumor suppressor gene cloned from LSCC [ 134 , 135 ].…”

Section: Mirnas In Regulating Cancer Stemnessmentioning

confidence: 99%

Roles of microRNAs in Regulating Cancer Stemness in Head and Neck Cancers

Fitriana

Hwang

Chan

et al. 2021

Cancers

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Head and neck squamous cell carcinomas (HNSCCs) are epithelial malignancies with 5-year overall survival rates of approximately 40–50%. Emerging evidence indicates that a small population of cells in HNSCC patients, named cancer stem cells (CSCs), play vital roles in the processes of tumor initiation, progression, metastasis, immune evasion, chemo-/radioresistance, and recurrence. The acquisition of stem-like properties of cancer cells further provides cellular plasticity for stress adaptation and contributes to therapeutic resistance, resulting in a worse clinical outcome. Thus, targeting cancer stemness is fundamental for cancer treatment. MicroRNAs (miRNAs) are known to regulate stem cell features in the development and tissue regeneration through a miRNA–target interactive network. In HNSCCs, miRNAs act as tumor suppressors and/or oncogenes to modulate cancer stemness and therapeutic efficacy by regulating the CSC-specific tumor microenvironment (TME) and signaling pathways, such as epithelial-to-mesenchymal transition (EMT), Wnt/β-catenin signaling, and epidermal growth factor receptor (EGFR) or insulin-like growth factor 1 receptor (IGF1R) signaling pathways. Owing to a deeper understanding of disease-relevant miRNAs and advances in in vivo delivery systems, the administration of miRNA-based therapeutics is feasible and safe in humans, with encouraging efficacy results in early-phase clinical trials. In this review, we summarize the present findings to better understand the mechanical actions of miRNAs in maintaining CSCs and acquiring the stem-like features of cancer cells during HNSCC pathogenesis.

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MIR106A-5p upregulation suppresses autophagy and accelerates malignant phenotype in nasopharyngeal carcinoma

Cited by 51 publications

References 56 publications

The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1

The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1

AMPK–mTOR–Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells

Roles of microRNAs in Regulating Cancer Stemness in Head and Neck Cancers

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