Knockdown of LncRNA-UCA1 Inhibits Breast Cancer Growth in Association with METTL14/miR-375/SOX12 Axis

Abstract Background Breast cancer is a malignant tumor with high incidence in females. Burgeoning studies have analyzed the relationship between long non-coding RNA (lncRNA) and breast cancer. However, the role of LncRNA UAC1 in the pathogenesis of breast cancer remains unclear. Methods LncRNA-UCA1 levels were detected in breast cancer tissues and cells while correlation between LncRNA-UCA1 expression and patient survival was analyzed by the Kaplan-Meier. The proliferation, invasion and apoptosis of cells were measured by CCK-8 assay, Transwell test and flow cytometry, respectively. Protein levels of apoptosis-related factors were assessed by Western blots. RIP test detected the combination of LncRNA-UCA1 and DNA methyltransferases whereas RNA pull-down test showed the interaction of DNA methyltransferases and LncRNA UCA1. Enrichment of DNA transferase of METTL14 promoter in T47D was assessed by ChIP. Interaction between miR-375 and SOX12 was confirmed via dual-luciferase reporter assay. Tumorigenesis was observed in vivo. Results LncRNA-UCA1 levels were increased in breast cancer and a high LncRNA-UCA1 level was a risk factor of the poor breast cancer prognosis. Silencing LncRNA-UCA1 inhibited the proliferation and invasion but promoted apoptosis of breast cancer cells. LncRNA-UCA1 recruited DNA methyltransferase to the METTL14 promoter region to inhibit METTL14 expression in breast cancer. Low METTL14 levels were associated with stronger proliferation and invasion abilities, whereas weaker proliferation and invasion abilities were related to low LncRNA-UCA1 levels. METTL14 mediated the low expression of miR-375 by m6A modification in breast cancer. Conclusion Depleted LncRNA-UCA1 inhibited breast cancer growth by regulating the METTL14-miR-375-SOX12 axis in vitro and in vivo.

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Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleotides to type I insulin-like growth factor receptor mRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity

Oncogene ◽

10.1038/sj.onc.1207659 ◽

2004 ◽

Vol 23 (30) ◽

pp. 5161-5174 ◽

Cited By ~ 46

Author(s):

Mariana Salatino ◽

Roxana Schillaci ◽

Cecilia J Proietti ◽

Romina Carnevale ◽

Isabel Frahm ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor Receptor ◽

Mapk Signaling ◽

Antisense Oligodeoxynucleotides ◽

Cancer Growth ◽

Type I ◽

Receptor Mrna ◽

Breast Cancer Growth ◽

Mapk Signaling Pathways

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IL-1 drives breast cancer growth and bone metastasis in vivo

Oncotarget ◽

10.18632/oncotarget.12289 ◽

2016 ◽

Vol 7 (46) ◽

pp. 75571-75584 ◽

Cited By ~ 71

Author(s):

Ingunn Holen ◽

Diane V. Lefley ◽

Sheila E. Francis ◽

Sarah Rennicks ◽

Steven Bradbury ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Cancer Growth ◽

Breast Cancer Growth

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MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000443033 ◽

2016 ◽

Vol 38 (2) ◽

pp. 777-785 ◽

Cited By ~ 24

Author(s):

Jian-Jun Sun ◽

Guo-Yong Chen ◽

Zhan-Tao Xie

Keyword(s):

Hepatocellular Carcinoma ◽

Nude Mice ◽

In Vivo Studies ◽

Luciferase Reporter ◽

Western Blots ◽

Normal Tissues ◽

Proliferation And Invasion ◽

Hcc Cells

Background/Aims: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). Methods: Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo. Results: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. Conclusion: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.

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Estrogen Deprivation and Inhibition of Breast Cancer Growth in Vivo through Activation of the Orphan Nuclear Receptor Liver X Receptor

Molecular Endocrinology ◽

10.1210/me.2007-0187 ◽

2007 ◽

Vol 21 (8) ◽

pp. 1781-1790 ◽

Cited By ~ 81

Author(s):

Haibiao Gong ◽

Ping Guo ◽

Yonggong Zhai ◽

Jie Zhou ◽

Hirdesh Uppal ◽

...

Keyword(s):

Breast Cancer ◽

Liver X Receptor ◽

Cancer Growth ◽

Estrogen Metabolism ◽

Endocrine Disorders ◽

Estrogen Deprivation ◽

Uterine Epithelial Cell ◽

Hepatic Expression ◽

Breast Cancer Growth

Abstract Estrogen plays an important role in normal physiology. It is also a risk factor for breast cancer, and antiestrogen therapies have been shown to be effective in the treatment and prevention of breast cancers. The liver is important for estrogen metabolism, and a compromised liver function has been linked to hyperestrogenism in patients. In this report, we showed that the liver X receptor (LXR) controls estrogen homeostasis by regulating the basal and inducible hepatic expression of estrogen sulfotransferase (Est, or Sult1e1), an enzyme critical for metabolic estrogen deactivation. Genetic or pharmacological activation of LXR resulted in Est induction, which in turn inhibited estrogen-dependent uterine epithelial cell proliferation and gene expression, as well as breast cancer growth in a nude mouse model of tumorigenicity. We further established that Est is a transcriptional target of LXR, and deletion of the Est gene in mice abolished the LXR effect on estrogen deprivation. Interestingly, Est regulation by LXR appeared to be liver specific, further underscoring the role of liver in estrogen metabolism. Activation of LXR failed to induce other major estrogen-metabolizing enzymes, suggesting that the LXR effect on estrogen metabolism is Est specific. In summary, our results have revealed a novel mechanism controlling estrogen homeostasis in vivo and may have implications for drug development in the treatment of breast cancer and other estrogen-related cancerous endocrine disorders.

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