miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

Lu, Yunjie; Gao, Junfang; Zhang, Shaopeng; Gu, Jian; Lü, Hao; Xia, Yongxiang; Zhu, Qi; Qian, Xiaofeng; Zhang, Feng; Zhang, Chuanyong; Shen, Hongbing; Hippen, Keli L.; Blazar, Bruce R.; Lü, Ling; Wang, Xuehao

doi:10.1038/s41419-018-0298-2

Cited by 40 publications

(29 citation statements)

References 54 publications

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“…ATG16L1 is a member of a large protein complex that is necessary for autophagy (22). As the expression of ATG16L1 was demonstrated to be increased at the mRNA and protein levels, we hypothesized that autophagy may be enhanced in SGC7901/DDP cells.…”

Section: Chemoresistant Gc Cells Exhibit Increased Autophagymentioning

confidence: 99%

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Huang¹,

Tang

Zhang

et al. 2018

Int J Oncol

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Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)-874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR-874 in MDR were investigated in GC. The overexpression of miR-874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy-related 16-like 1 (ATG16 L1) was identified as a direct target of miR-874. ATG16L1 was also demonstrated to be positively associated with autophagy. Reducing the expression of ATG16L1 and inhibiting the occurrence of autophagy sensitized GC cells to chemotherapy. Thus, the miR-874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR-874 may be used as a prognostic factor in GC. Overall, miR-874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR-874 in chemotherapeutic resistance.

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Section: Chemoresistant Gc Cells Exhibit Increased Autophagymentioning

confidence: 99%

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Huang¹,

Tang

Zhang

et al. 2018

Int J Oncol

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“…ULK phosphorylates Beclin-1 following amino acid withdrawal, and this phosphorylation step is crucial for the function of Beclin-1 in autophagy [17,18]. Previously, miR-142-3p was reported to target ATG-1 (ATG16L1) [19]. Here, online tools predicted that miR-142 and miR-22 might target ULK and that miR-142 may target ATG4A and ATG5.…”

Section: Mir-22/mir-142 Targets Key Autophagy Proteins Atg5 Atg4a Anmentioning

confidence: 86%

“…miR-142-3p overexpression increases the chemosensitivity of nonsmall-cell lung cancer by inhibiting HMGB1-mediated autophagy [35]. MiR-142-3p inhibits autophagy by targeting ATG16L1 in thymic-derived regulatory T cells [14,19]. As predicted by online tools and validated by luciferase reporter assays, miR-142 directly targets ULK1, ATG4A, and ATG5, and miR-22 directly targets ULK1.…”

Section: Agingmentioning

confidence: 90%

LncRNA Sox2OT-V7 promotes doxorubicin-induced autophagy and chemoresistance in osteosarcoma via tumor-suppressive miR-142/miR-22

Zhu

Yang

Wen

et al. 2020

Aging

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Doxorubicin (Dox) is one of the most commonly used chemotherapeutic drugs for osteosarcoma (OS) treatment. In the present study, we attempted to investigate the mechanism by which Sox2OT-V7 dysregulation affects Dox chemoresistance to provide a novel experimental basis for developing neoadjuvant therapy. Sox2OT-V7 expression is upregulated in OS tissues, particularly in chemoresistant OS tissues, and in OS cell lines compared to controls. Dox treatment induces autophagy and Sox2OT-V7 expression in U2OS cells, and Dox-induced autophagy is partially attenuated by Sox2OT-V7 silencing. Knocking down Sox2OT-V7 or blocking autophagy in Dox-resistant U2OS/Dox cells resensitizes the cells to Dox treatment in vitro. Moreover, Sox2OT-V7 directly targets miR-142/miR-22 to inhibit their expression, and the effect of Sox2OT-V7 silencing on U2OS cell autophagy and U2OS/Dox cell sensitivity to Dox can be reversed by miR-142/miR-22 inhibition. Sox2OT-V7 silencing enhances the suppressive effects of Dox on U2OS/Dox cell-derived tumor growth in vivo, while miR-22 inhibition or miR-142 inhibition reverses the effects of Sox2OT-V7 silencing on Dox-induced suppression on tumor growth. Finally, miR-142 directly targets ULK1, ATG4A, and ATG5, while miR-22 directly targets ULK1 to inhibit the expression of the target gene; The Sox2OT-V7/miR-142/miR-22 axis modulates autophagy in OS cells by regulating ULK1, ATG4A, and ATG5.

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“…Studies revealed that miRNAs were aberrantly expressed at different stages of melanoma, and they have been identified as potential diagnostic and prognostic biomarkers (Ross, Kaushik, Valdes‐Rodriguez, & Anvekar, ). miR‐142‐3p is a tumor suppressor in many tumors and it can regulate autophagy (Y. Lu et al, ; Mansoori et al, ). Tembe et al () found that miR‐142‐3p was abnormally expressed in melanoma tissues.…”

Section: Discussionmentioning

confidence: 99%

Licochalcone A restrains microphthalmia‐associated transcription factor expression and growth by activating autophagy in melanoma cells via miR‐142‐3p/Rheb/mTOR pathway

Zhang

Gao

Chen

et al. 2019

Phytotherapy Research

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Licochalcone A (LCA) was found to possess anticancer effects. This study aimed to investigate the anticancer effects and mechanisms of LCA in melanoma. A375 and B16 melanoma cells were stimulated with LCA, MTT assay was used to assess cell proliferation. Expression of miR-142-3p, microphthalmia-associated transcription factor (MITF, which regulates melanin production) and autophagy-related genes was determined by Real-time PCR or western blot. The apoptosis was analyzed by flow cytometry and caspase-3 activity. The roles of miR-142-3p and Ras homolog enriched in brain (Rheb) in LCA-affected cells were investigated by gain-and loss-of functions. LCA inhibited proliferation and MITF expression, but increased apoptosis and autophagy of melanoma cells. Moreover, LCA elevated miR-142-3p expression, but decreased its target gene Rheb expression. The effects of LCA on melanoma cells were abrogated by miR-142-3p inhibitor or Rheb overexpression. LCA suppressed mTOR signaling activation via Rheb. Additionally, rapamycin (a mTOR antagonist) notably attenuated the effects of Rheb on the autophagy, proliferation, apoptosis, and MITF expression in LCA-treated melanoma cells. In conclusion, LCA restrained MITF expression and growth by activating autophagy in melanoma cells via miR-142-3p/Rheb/mTOR pathway. This study suggested that LCA might be a potential therapeutic candidate for prevention and treatment of melanoma. K E Y W O R D Sautophagy, Licochalcone A, melanoma, miR-142-3p/Rheb/mTOR

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miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg)

Cited by 40 publications

References 54 publications

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

LncRNA Sox2OT-V7 promotes doxorubicin-induced autophagy and chemoresistance in osteosarcoma via tumor-suppressive miR-142/miR-22

Licochalcone A restrains microphthalmia‐associated transcription factor expression and growth by activating autophagy in melanoma cells via miR‐142‐3p/Rheb/mTOR pathway

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