Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling

Mo, Pingli; Zhou, Qiling; Guan, Lei; Wang, Yi; Wang, Wei; Miao, Mengmeng; Tong, Zhangwei; Li, Ming; Majaz, Sidra; Liu, Yonghong; Su, Guoqiang; Xu, Jianming; Yu, Chundong

doi:10.1038/onc.2014.324

Cited by 32 publications

(38 citation statements)

References 46 publications

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“…9 MiR-17 and miR-20b mimics, inhibitors and negative control (NC) were purchased from GenePharma (Shanghai, China). Cells were trypsinised, counted and seeded into six-well plates the day before transfection to ensure 70% cell confluence on the day of transfection.…”

Section: Methodsmentioning

confidence: 99%

“…10 An oncogenic role of NCOA3 has also been found in other cancer types, such as prostate, ovarian, esophageal, gastric, colon and liver cancers. 9, 11 Previous study show high expression of NCOA3 promote tamoxifen resistance by increasing ER activity in breast cancer. 12 Whereas another study indicates that patients with high nuclear expression of NCOA3 tend to respond well to tamoxifen therapy.…”

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confidence: 98%

“…7 NCOA3 has been found to have important role in a number of biological processes, such as cell proliferation, apoptosis and migration. 8, 9 NCOA3 gene amplification has been found in 2–10% of human breast cancer. 10 Moreover, NCOA3 is overexpressed in 30–60% breast cancer and associated with high histological grade, advanced stage and poor prognosis.…”

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confidence: 99%

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Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

Nie

et al. 2016

Cell Death Dis

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Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. In this study, nuclear receptor coactivator 3 (NCOA3) was found to be significantly increased in taxol-resistant breast cancer tissues and cells. Moreover, overexpression of NCOA3 enhanced breast cancer cell resistance to taxol, whereas depletion of NCOA3 decreased taxol resistance. Subsequently, we investigated whether NCOA3 expression was regulated by miRNAs in breast cancer. By bioinformatics prediction in combination with the data of previous report, miR-17 and miR-20b were selected as the potential miRNAs targeting NCOA3. By real-time PCR analysis, we found that miR-17 and miR-20b were significantly reduced in taxol-resistant breast cancer tissues and cells. In addition, we provided some experimental evidences that miR-17 and miR-20b attenuated breast cancer resistance to taxol in vitro and in vivo models. Furthermore, by luciferase reporter assays, we further validated that both miR-17 and miR-20b directly binded the 3′-untranslated region of NCOA3 mRNA and inhibited its expression in breast cancer cells. Finally, both miR-17 and miR-20b levels were found to be significantly negatively correlated with NCOA3 mRNA levels in breast cancer tissues. Together, our results indicated that loss of miR-17 and miR-20b enhanced breast cancer resistance to taxol by upregulating NCOA3 levels. Our study suggested miR-17, miR-20b and NCOA3 may serve as some predictive biomarkers and potential therapeutic targets in taxol-resistant breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

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confidence: 98%

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Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

Nie

et al. 2016

Cell Death Dis

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“…Accumulating evidence shows that NCOA3 is highly expressed in a various human cancers (Anzick et al ., ; Xu et al ., ; Zhou et al ., ), and it can interact with nuclear receptors and other transcription factors to regulate the expression of their target genes involved in many signaling pathways, including EGFR, Akt, MAPK, E2F1, and Notch (Long et al ., ; Louie et al ., ; Mo et al ., ; Yan et al ., ). However, little is known about how NCOA3 is regulated in colorectal cancer (CRC).…”

Section: Discussionmentioning

confidence: 99%

MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and degradation

Chen

et al. 2018

Molecular Oncology

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Nuclear receptor coactivator 3 (NCOA3) is a transcriptional coactivator that has elevated expression in multiple tumor types, including colorectal cancer (CRC). However, the molecular mechanisms that regulate the tumorigenic functions of NCOA3 in CRC remain largely unknown. In this study, we aimed to discover and identify the novel regulatory proteins of NCOA3 and explore their mechanisms of action. Immunoprecipitation (IP) coupled with mass spectrometry (IP‐MS) analysis was used to detect, identify, and verify the proteins that interacted with NCOA3 in CRC cells. The biological functions of the candidate proteins and the underlying molecular mechanism were investigated in CRC cells and mouse model in vitro and in vivo. The clinical significance of NCOA3 and its interaction partner protein in CRC patients was also studied. We identified mitotic arrest deficient 2‐like protein 2 (MAD2L2, also known as MAD2B or REV7), with two signal peptide sequences of LIPLK and EVYPVGIFQK, to be an interaction partner of NCOA3. Overexpression of MAD2L2 suppressed the proliferation, migration, and clonogenicity of CRC cells by inducing the degradation of NCOA3. The mechanism study showed that increased MAD2L2 expression in CRC cells activated p38, which was required for the phosphorylation of NCOA3 that led to its ubiquitination and degradation by the proteasome. Moreover, we found that MAD2L2 predicted favorable prognosis in CRC patients. We have discovered a novel role of MAD2L2 in the regulation of NCOA3 degradation and proposed that MAD2L2 serves as a tumor suppressor in CRC.

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“…Early on, SRC-3 was found to be amplified in ovarian cancer (8, 9) and elevated SRC-3 expression has been found in 64% of high-grade ovarian cancers, and its levels are correlated with tumor progression (37). SRCs also have been implicated in a wide variety of cancers including pancreatic (38, 39), colon (40), lung (41) and other cancers (2). …”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: Targeting Steroid Receptor Coactivators in Cancer

Lonard

O’Malley

2016

Clinical Cancer Research

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Coactivators represent a large class of proteins that partner with nuclear receptors (NRs) and other transcription factors to regulate gene expression. Given their pleiotropic roles in the control of transcription, coactivators have been implicated in a broad range of human disease states, including cancer. This is best typified by the three members of the steroid receptor coactivator (SRC) family, each of which integrates steroid hormone signaling and growth factor pathways to drive oncogenic gene expression programs in breast, endometrial, ovarian, prostate and other cancers. Because of this, coactivators represent emerging targets for cancer therapeutics and efforts are now being made to develop SRC-targeting agents such as the SI-2 inhibitor and the novel SRC stimulator, MCB-613, that are able to block cancer growth in cell culture and animal model systems. Here, we will discuss the mechanisms through which coactivators drive cancer progression and how targeting coactivators represent a novel conceptual approach to combat tumor growth that is distinct from the use of other targeted therapeutic agents. We also will describe efforts to develop next-generation SRC inhibitors and stimulators that can be taken into the clinic for the treatment of recurrent, drug-resistant cancers.

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Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling

Cited by 32 publications

References 46 publications

Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and degradation

Molecular Pathways: Targeting Steroid Receptor Coactivators in Cancer

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