Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis

Liang, Hongjun; Xiao, Jianru; Zhou, Zhongmei; Wu, Jiao; Ge, Fei; Li, Zongcheng; Zhang, Hailin; Sun, Jian; Li, Fubing; Liu, Rong; Chen, Ceshi

doi:10.1038/s41388-017-0089-8

Cited by 115 publications

(98 citation statements)

References 44 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR‐153 is proposed as a newfangled tumor‐correlative miRNA, which has been discovered to be dramatically deregulated in tumors (Bai et al, ; Chen et al, ). A research by Liang et al () promulgated that hypoxia management could engender the enhancement of miR‐153, thereby affecting breast cancer angiogenesis. Additionally, the evidence from He et al () revealed that propofol could enhance miR‐153 expression in hypoxia‐impaired PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

“…A research has reported that aberrant expressed miR‐153 was linked to overexpression of hypoxia‐inducible factor‐1α in refractory epilepsy (Li et al, ). Moreover, other research revealed that hypoxia triggered miR‐153 via IRE1α‐XBP1 pathway and HIF1α/VEGFA axis in breast cancer angiogenesis (Liang et al, ). Therefore, we speculated that GAA affected miR‐153 expression through adjusting some hypoxia correlative factors and pathways.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Lou

Zhang

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Ganoderic Acid A (GAA) is often applied for healing cardiovascular and cerebrovascular ailments, but the influences in cerebral ischemia injury are still hazy. The research delved into the functions of GAA in hypoxia‐triggered impairment in PC12 cells. PC12 cells received hypoxia management for 12 hr, and subsequently, cell viability, migration, apoptosis, and correlative protein levels were assessed. After preprocessing with GAA, above cell behaviors were monitored again. The vector of microRNA (miR)‐153 inhibitor was utilized for PC12 cell transfection to further explore the functions of miR‐153 in hypoxia‐impaired cells. Pathways of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were investigated via executing western blot for uncovering the latent mechanism. Results revealed that hypoxia disposition triggered PC12 cells impairment via restraining cell viability and migration and accelerating apoptosis. However, GAA visibly mollified hypoxia‐provoked impairment in PC12 cells. Interestingly, the enhancement of miR‐153 triggered by GAA was observed in hypoxia‐impaired PC12 cells. After miR‐153 inhibitor transfection, the protective functions of GAA in hypoxia‐impaired PC12 cells were dramatically inversed. Furthermore, GAA caused PI3K/AKT and mTOR activations via enhancement of miR‐153 in hypoxia‐impaired PC12 cells. The findings evinced that GAA exhibited the protective functions in PC12 cells against hypoxia‐evoked impairment through activating PI3K/AKT and mTOR via elevating miR‐153.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Lou

Zhang

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…Apart from this, miRNA-21a participates in the regulation of EC metabolism also. The expression of miRNA-153 is induced by hypoxia-induced ER stress in BC angiogenesis However, it has an anti-angiogenic action by down-regulating VEGFA secretion [70]. Hence miRNA-153 fine tunes HIF-1α/VEGFA axis in BC angiogenesis.…”

Section: Angiomirs Responsive To Oxygen Levelmentioning

confidence: 99%

“…Hence miRNA-153 fine tunes HIF-1α/VEGFA axis in BC angiogenesis. Moreover, miRNA-153 has targets against several other oncogenes associated with survival (HECTD3) [129], EMT (MTDH) [71] and stemness (nuclear factor, erythroid 2 like 2 (NRF2)) [70]. The expression of miRNA-497 is deregulated in breast cancer cells in comparison to normal breast cell line.…”

Section: Angiomirs Responsive To Oxygen Levelmentioning

confidence: 99%

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

et al. 2020

View full text Add to dashboard Cite

Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.

show abstract

“…The presence of misfolded proteins is sensed via 3 transmembrane proteins in the ER: IRE1α, PERK and ATF6a. Actors of the ER-stress pathways have been described to play a role in the progression of solid tumors, such as breast cancer 33 , colon cancer 32 and HCC 50 . Activation of the UPR has also been implicated in the pathogenesis of non-alcoholic fatty liver disease 7, 28, 29 , hepatitis B-induced carcinogenesis 30 and biliary cirrhosis 41 .…”

Section: Introductionmentioning

confidence: 99%

Inhibiting endoplasmic reticulum stress decreases tumor burden in a mouse model for hepatocellular carcinoma

Pavlović

Calitz

Thanapirom

et al. 2019

Preprint

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a liver tumor that arises in patients with cirrhosis. Hepatic stellate cells are key players in the progression of HCC, as they create a fibrotic micro-environment and produce growth factors and cytokines that enhance tumor cell proliferation and migration. We assessed the role of endoplasmic reticulum (ER) stress in the cross-talk between stellate cells and HCC-cells. Mice with a fibrotic HCC were treated with the IRE1α-inhibitor 4μ8C, which reduced tumor burden and collagen deposition. By co-culturing HCC-cells with stellate cells, we found that HCC-cells induce ER-stress in stellate cells, thereby contributing to their activation. Inhibiting IRE1α blocked stellate cell activation, which inhibited tumor cell proliferation and migration in different in vitro 2D and 3D co-cultures. Our results suggest that IRE1α is an important mediator in the communication between stellate cells and cancer cells and components of the ER-stress pathway may be therapeutically relevant for HCC-patients.Impact statementIRE1α is an important mediator in the communication between stellate cells and cancer cells and components of the ER-stress pathway may be therapeutically relevant for liver cancer.

show abstract

Hypoxia induces miR-153 through the IRE1α-XBP1 pathway to fine tune the HIF1α/VEGFA axis in breast cancer angiogenesis

Cited by 115 publications

References 44 publications

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Retracted: Ganoderic Acid A exerts the cytoprotection against hypoxia‐triggered impairment in PC12 cells via elevating microRNA‐153

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

Inhibiting endoplasmic reticulum stress decreases tumor burden in a mouse model for hepatocellular carcinoma

Contact Info

Product

Resources

About