Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway

Xie, Xiaolei; Man, Xian; Zhu, Zuobin; Yuan, Dejian; Huang, Shi

doi:10.1002/oby.21364

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…Because S100A4 is a small molecular protein, we conjecture that S100A4 inhibits obesity development via collaborating with other intracellular proteins or transcription factors. On this point, S100A4 has been reported to affect various protein kinases, especially Akt, which is not only a well-recognized tumor modulator but also an adipogenesis regulator [41,42]. This study displayed that S100A4 stimulates activation of the Akt pathway (the key insulin-related pathway) during HFDinduced obesity.…”

Section: Discussionmentioning

confidence: 67%

S100A4 protects mice from high-fat diet-induced obesity and inflammation

Hou

Jiao

et al. 2018

Laboratory Investigation

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As a member from S100 calcium-binding protein family, S100A4 is ubiquitous and elevated in tumor progression and metastasis, but its role in regulating obesity has not been well characterized. In this study, we showed that S100A4 was mainly expressed by stromal cells in adipose tissue and the S100A4 level in adipose tissue was decreased after high-fat diet (HFD). S100A4 deficient mice exhibited aggravated symptoms of obesity and suppressed insulin signaling after 12 weeks of HFD. Aggravated obesity in S100A4 deficient mice were found to be positively correlated with higher inflammatory status of the liver. Then, we found that extracellular S100A4 or overexpressed S100A4 inhibited adipogenesis and decreased mRNA levels of inflammation gene in 3T3-L1 adipocytes in vitro; whereas small interfering RNA (siRNA)-mediated suppression of S100A4 displayed the opposite results. Additionally, the protective effect induced by S100A4 during HFD-induced obesity was tightly related with activation of Akt signaling in adipose tissues, as well as livers and muscles. Taken together, we demonstrate that S100A4 is an inhibitory factor for obesity and attenuates the inflammatory reaction, while activating the Akt signaling, which suggest that S100A4 is a potential candidate for the treatment of diet-induced obesity and its complications.

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Section: Discussionmentioning

confidence: 67%

S100A4 protects mice from high-fat diet-induced obesity and inflammation

Hou

Jiao

et al. 2018

Laboratory Investigation

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“…Consistently, miR-532 overexpression has been reported to inhibit activation of the PI3K/AKT signaling pathway in colorectal cancer in vitro and in vivo (38). The positive correlation between AKT3 and the PI3K/ AKT signaling pathway has been well-established (39,40). Blockade of the PI3K/AKT signaling pathway by dammarenediol contributes to a decline in the viability of osteosarcoma cells and their metastatic potential (41).…”

Section: Discussionmentioning

confidence: 98%

CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis

2021

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Emerging evidence indicates that extracellular vesicle (EV)-encapsulated circRNAs have the potential diagnostic and prognostic values for malignancies. However, the role of circNRIP1 in osteosarcoma remains unclear. We herein investigated the therapeutic potential of circNRIP1 delivered by bone marrow mesenchymal stem cell–derived EVs (BMSC-EVs) in osteosarcoma. The expression of circNRIP1 was examined in the clinical tissue samples of osteosarcoma patients, after which the downstream genes of circNRIP1 were bioinformatically predicted. Gain- and loss-of function assays were then performed in osteosarcoma cells with manipulation of circNRIP1 and miR-532-3p expression. EVs isolated from BMSCs were characterized and co-cultured with osteosarcoma cells to examine their effects on cell phenotypes, as reflected by CCK-8 and Transwell assays. Further, a mouse model of tumor xenografts was established for in vivo substantiation. circNRIP1 was upregulated in osteosarcoma tissues and cells. Overexpression of circNRIP1 promoted the proliferative, migratory, and invasive potential of osteosarcoma cells. Co-culture data showed that BMSC-EVs could transfer circNRIP1 into osteosarcoma cells where it competitively bound to miR-532-3p and weakened miR-532-3p’s binding ability to AKT3. By this mechanism, the PI3K/AKT signaling pathway was activated and the malignant characteristics of osteosarcoma cells were stimulated. In vivo experimental results unveiled that circNRIP1-overexpressing BMSC-EVs in nude mice resulted in enhanced tumor growth. In conclusion, the BMSC-EV-enclosed circNRIP1 revealed a new molecular mechanism in the pathogenesis of osteosarcoma, which might provide a novel therapeutic target for osteosarcoma.

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“…Especially, the PI3K/Akt/mTOR signaling pathways were demonstrated to regulate autophagy under certain conditions. [7,8] However, the role of autophagy was still not fully understood in hypoxic pulmonary hypertension (HPAH).…”

Section: Introductionmentioning

confidence: 99%

NPS2390, a selective calcium-sensing receptor antagonist controls the phenotypic modulation of hypoxic human pulmonary arterial smooth muscle cells by regulating autophagy

Xue

Wei

et al. 2019

Journal of Translational Internal Medicine

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Background and Objectives Calcium-sensing receptor (CaSR) is known to regulate hypoxia-induced pulmonary hypertension (HPH) and vascular remodeling via the phenotypic modulation of pulmonary arterial smooth muscle cells (PASMCs) in small pulmonary arteries. Moreover, autophagy is an essential modulator of VSMC phenotype. But it is not clear whether CaSR can regulate autophagy involving the phenotypic modulation under hypoxia. Methods The viability of human PASMCs was detected by cell cycle and BrdU. The expressions of proliferation protein, phenotypic marker protein, and autophagy protein in human PASMCs were determined by western blot. Results Our results showed that hypoxia-induced autophagy was considerable at 24 h. The addition of NPS2390 decreased the expression of autophagy protein and synthetic phenotype marker protein osteopontin and increased the expression of contractile phenotype marker protein SMA-ɑ and calponin via suppressing downstream PI3K/Akt/mTOR signal pathways. Conclusions Our study demonstrates that treatment of NPS2390 was conducive to inhibit the proliferation and reverse phenotypic modulation of PASMCs by regulating autophagy levels.

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Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway

Cited by 9 publications

References 39 publications

S100A4 protects mice from high-fat diet-induced obesity and inflammation

S100A4 protects mice from high-fat diet-induced obesity and inflammation

CircNRIP1 Encapsulated by Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Vesicles Aggravates Osteosarcoma by Modulating the miR-532-3p/AKT3/PI3K/AKT Axis

NPS2390, a selective calcium-sensing receptor antagonist controls the phenotypic modulation of hypoxic human pulmonary arterial smooth muscle cells by regulating autophagy

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