Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Xu, Chongwen; Sun, Xin; Qin, Sida; Wang, Huangzhen; Zheng, Zeqi; Xu, Shaohua; Luo, Gang; Liu, Peng; Liu, Jian; Du, Ning; Zhang, Yunfeng; Liu, Dapeng; Ren, Hong

doi:10.1080/15384101.2015.1030547

Cited by 46 publications

(38 citation statements)

References 58 publications

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“…let-7a-5p, the firstly identified tumor repressing miRNA, can modulate a large number of oncogenes to suppress tumor progression by binding the 3 0 -untranslated region (3 0 -UTR) of the target mRNAs, including Ras, MYC and HMGA2. [15][16][17] let-7a-5p was reported to be poorly expressed in colorectal cancer, which could be utilized to predict lymph node metastasis and the disease prognosis. 18 In breast cancer, let-7a-5p was downregulated.…”

Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Liu

Tai

2018

Cancer Biology & Therapy

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The long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be upregulated and be involved in oncogenic growth and drug resistance in nasopharyngeal carcinoma (NPC). However, the exact roles of NEAT1 and its underlying mechanisms in the drug resistance of NPC remain largely unclear. In this study, the expressions of NEAT1, let-72-5p and Rsf-1 mRNA were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of NEAT1 and let-72-5p on cell proliferation and cisplatin resistance of NPC cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-20-deoxyuridine (EdU) assay. Western blot analysis was performed to detect the protein levels of Rsf-1, Ras, p-Raf1, Raf1, p-MEK1, MEK1, p-ERK1/2 and ERK1/2. Xenograft tumor assay was done to elucidate the role of NEAT1 involved in NPC tumor growth in vivo. We found that NEAT1 was upregulated and let-7a-5p was downregulated in NPC tissues, as well as NPC cell lines. Inhibition of NEAT1 markedly repressed the cisplatin resistance of NPC cells. NEAT1 was demonstrated to interact with let-7a-5p. Besides, a negative correlation between NEAT1 and let-7a-5p expression was observed in NPC tissues. Rsf-1 was confirmed as a target of let-7a-5p. NEAT1 remarkably reversed the inhibitory effect of let-7q-5p on the cisplatin resistance of NPC cells in vitro. Additionally, NEAT1 knockdown inhibited the Ras-MAPK pathway in NPC cells. NEAT1 knockdown suppressed tumor growth in the presence of cisplatin in vivo. Overall, these findings suggest that NEAT1/let-7a-5p axis regulates the cisplatin resistance in NPC by targeting Rsf-1 and modulating the Ras-MAPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Liu

Tai

2018

Cancer Biology & Therapy

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“…HER2-overexpressing BCSCs are causally associated with an aggressive phenotype and radiotherapy resistance [19]. HER2 regulates BCSCs through several signaling pathways, such as the PI3K/AKT, Wnt [21, 53], and MAPK/ERK pathways [54, 55]. In HER2-positive breast cancers, HER2 interacts with CXCR1, which is selectively expressed in BCSCs [56].…”

Section: Discussionmentioning

confidence: 99%

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells

Zhang¹,

Chen²,

Gong³

et al. 2018

Cell Physiol Biochem

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Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.

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“…Activation of TLR3 was also shown to induce the co-activation of β-catenin and NF-ƘB, leading to the promotion of breast CSCs [156]. In addition to various signaling molecules, miRNAs also induce CSCs by activating NF-κB pathway; for instance, Let7a induces mammosphere formation by activating the Ras/ NF-κB pathway [157]. …”

Section: Maintenance Of “Cancer Stemness”mentioning

confidence: 99%

Unraveling the journey of cancer stem cells from origin to metastasis

Nimmakayala

Batra

Ponnusamy

2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Cancer biology research over recent decades has given ample evidence for the existence of self-renewing and drug-resistant populations within heterogeneous tumors, widely recognized as cancer stem cells (CSCs). However, a lack of clear understanding about the origin, existence, maintenance, and metastatic roles of CSCs limit efforts towards the development of CSC-targeted therapy. In this review, we describe novel avenues of current CSC biology. In addition to cell fusion and horizontal gene transfer, CSCs are originated by mutations in somatic or differentiated cancer cells, resulting in de-differentiation and reprogramming. Recent studies also provided evidence for the existence of distinct or heterogeneous CSC populations within a single heterogeneous tumor. Our analysis of the literature also opens the doors for a novel hypothesis that CSC populations with specific phenotypes, metabolic profiles, and clonogenic potential metastasize to specific organs.

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Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Cited by 46 publications

References 58 publications

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

LncRNA NEAT1/let-7a-5p axis regulates the cisplatin resistance in nasopharyngeal carcinoma by targeting Rsf-1 and modulating the Ras-MAPK pathway

Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells

Unraveling the journey of cancer stem cells from origin to metastasis

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