LncRNA NKILA suppresses TGF-β-induced epithelial-mesenchymal transition by blocking NF-κB signaling in breast cancer

Wu, Wei; Chen, Fei; Cui, Xiuying; Yang, Limei; Chen, Jianing; Zhao, Jinghua; Huang, Di; Liu, Jiang; Yang, Linbin; Zeng, Jiayi; Zeng, Zhiqing; Pan, Yunbao; Su, Fengxi; Cai, Junchao; Ying, Zhongfu; Zhao, Qiyi; Song, Erwei; Su, Shicheng

doi:10.1002/ijc.31605

Cited by 90 publications

(135 citation statements)

References 54 publications

(135 reference statements)

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“…Previous studies indicate that stimulating EMT and increasing CSCs can promote cancer metastasis and relapse . Cells undergoing EMT are known to acquire stem cell‐like properties.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies indicate that stimulating EMT and increasing CSCs can promote cancer metastasis and relapse. 34,[47][48][49][50] Cells undergoing EMT are known to acquire stem cell-like properties. Loss of epithelial marker E-cadherin, increased expression of mesenchymal markers Fibronectin and Vimentin and the EMT regulator Snail, which are important events in EMT.…”

Section: Discussionmentioning

confidence: 99%

Highly‐expressed P2X7 receptor promotes growth and metastasis of human HOS/MNNG osteosarcoma cells via PI3K/Akt/GSK3β/β‐catenin and mTOR/HIF1α/VEGF signaling

et al. 2019

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The P2X7 receptor, an ATP‐gated ion channel, is critical for cancer cell growth, invasiveness, and angiogenesis. Previous studies indicate that P2X7 regulates osteoblast proliferation and osteodeposition and that high P2X7 expression has a pro‐growth effect in osteosarcoma. However, how it functions in osteosarcoma cell growth and metastasis is not clear. Thus, we elucidated molecular mechanisms of P2X7‐dependent positive regulation of osteosarcoma cell proliferation, invasion, migration, epithelial to mesenchymal transition (EMT), and angiogenesis using in vitro and in vivo models. We confirm that P2X7 is highly‐expressed in human osteosarcoma tumor tissues and HOS/MNNG, MG63, U2OS, SW1353 and SAOS‐2 cell lines. P2X7 receptor stimulation enhanced HOS/MNNG and SAOS‐2 cell proliferation, migration and invasion; but knockdown of P2X7 expression or receptor inhibition had opposite effects. P2X7 positively regulated glycogen content, epithelial to mesenchymal transition and stemness of HOS/MNNG cells. P2X7 activation promoted PI3K/Akt/GSK3β/β‐catenin and mTOR/HIF1α/VEGF signaling, thereby mediating pro‐tumor effects of osteosarcoma cells. Consistent with data from in vitro experiments, systemic administration of P2X7 agonist induced tumor growth, metastasis and tumor‐associated bone destruction in osteosarcoma‐bearing nude mice, whereas a P2X7 antagonist reversed these effects. Thus, the P2X7 receptor participates in regulation of osteosarcoma growth and metastasis and we offer evidence that P2X7 may be a promising therapeutic target for treating osteosarcoma.

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“…346 Activation of TGF-β1 induces lncRNA NKILA expression to block NF-κB signaling, which inhibits metastasis of breast CSCs. 412 TGF-β also directly regulates the expression of Wnt5a in breast CSCs to limit the stem cell population. 413 Furthermore, Notch, IKK/NF-κB, and other pathways together regulate the proliferation and metastasis of CD133 + cutaneous SCC stem cells.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

Self Cite

678

648

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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“…Notch signaling was also proved to promote HER2 + breast cancer cell proliferation and stem cell survival. [40][41][42] However, we future molecular and large scale, multicenter studies should be designed to analyze the exact mechanisms that USP8 regulate the proliferation of BC. Meanwhile, lots of studies have shown that epithelial-mesenchymal transition played an important role in the progression of BC.…”

Section: Discussionmentioning

confidence: 99%

The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer

Qiu

Kong

Cheng

et al. 2018

J of Cellular Biochemistry

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“…[17][18][19][20] Long non-coding RNAs (lncRNAs), which are a subset of non-coding transcripts with more than 200 nucleotides in length, have been reported to have regulatory roles in numerous cellular disorders, such as inflammation, immunity and various cancers. [21][22][23][24][25] However, the roles of lncRNAs in osteogenic regulation are poorly defined.…”

Section: Introductionmentioning

confidence: 99%

LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP‐1 signalling‐mediated RUNX2 expression

Peng

et al. 2019

J Cell Mol Med

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Mesenchymal stem cells (MSCs) have potential ability to differentiate into osteocytes in response to in vitro specific induction. However, the molecular basis underlying this biological process remains largely unclear. In this study, we identify lncRNA HOTAIRM1 as a critical regulator to promote osteogenesis of MSCs. Loss of HOTAIRM1 significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. Mechanistically, we find that HOTAIRM1 positively modulates the activity of JNK and c‐Jun, both of which are widely accepted as crucial regulators of osteogenic differentiation. More importantly, c‐Jun is found to be functionally involved in the regulation of RUNX2 expression, a master transcription factor of osteogenesis. In detail, c‐Jun can help recruit the acetyltransferase p300 to RUNX2 promoter, facilitating acetylation of histone 3 at K27 site, therefore epigenetically activating RUNX2 gene transcription. In summary, this study highlights the functional importance of HOTAIRM1 in regulation of osteogenesis, and we characterize HOTAIRM1 as a promising molecular target for bone tissue repair and regeneration.

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LncRNA NKILA suppresses TGF-β-induced epithelial-mesenchymal transition by blocking NF-κB signaling in breast cancer

Cited by 90 publications

References 54 publications

Highly‐expressed P2X7 receptor promotes growth and metastasis of human HOS/MNNG osteosarcoma cells via PI3K/Akt/GSK3β/β‐catenin and mTOR/HIF1α/VEGF signaling

Targeting cancer stem cell pathways for cancer therapy

The expression of ubiquitin‐specific peptidase 8 and its prognostic role in patients with breast cancer

LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP‐1 signalling‐mediated RUNX2 expression

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