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      MiR-940 promotes malignant progression of breast cancer by regulating FOXO3

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          Abstract

          Breast cancer (BC) is a common cancer with poor survival. The present study aimed to explore the effect of miR-940 on the process of BC cells and its target gene FOXO3. The expression of miR-940 was assessed in BC tissues and cells using qRT-PCR. Furthermore, the correlation between miR-940 and prognosis of BC patients from the TCGA database was analyzed. CCK8 assays and colony formation assays were used to explore the effect of miR-940 on BC cell proliferation. The invasion abilities were detected by transwell assays. Luciferase reporter assay was performed to scrutinize the relationship between miR-940 and FOXO3. Finally, rescue experiments were performed through FOXO3 down-regulation and miR-940 inhibitors by using CCK8 assays, colony formation assays and transwell assays. miR-940 was significantly up-regulated in BC cells and tissues. In addition, the high level of miR-940 correlated with poor survival of BC patients ( P=0.023). CCK8 assays, colony formation assays and transwell assays indicated that miR-940 promoted the proliferation and invasion abilities of BC cells. The luciferase reporter assay suggested that miR-940 directly targeted FOXO3. Moreover, we found that the effect of si-FOXO3 was rescued by miR-940 inhibitors in BC cells. miR-940 may promote the proliferation and invasion abilities of BC cells by targeting FOXO3. Our study suggested that miR-940 could be a novel molecular target for therapies against BC.

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          Most cited references10

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          FOXOs, cancer and regulation of apoptosis.

          Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein-protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondria-independent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-X(L), respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer.
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            Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A

            Significance Prostate cancer is one of most common cancers in men worldwide, and osteoblastic bone metastasis is frequently observed in prostate cancer patients. However, the mechanisms responsible for the predominantly osteoblastic phenotype have not been fully elucidated. Cancer-secreted microRNAs (miRNAs) were recently shown to be significant in the modification of the tumor microenvironment. Here, hsa-miR-940, which was highly secreted by prostate cancer cells, promoted osteogenic differentiation of human mesenchymal stem cells in vitro, and induced extensive osteoblastic lesions in the bone metastatic microenvironment in vivo. Our study provides a demonstration that osteoblastic bone metastasis can be induced by miRNAs secreted by cancer cells in the bone microenvironment.
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              MiR-150 promotes gastric cancer proliferation by negatively regulating the pro-apoptotic gene EGR2.

              Accumulating evidence suggests small non-coding RNAs (microRNAs) play important roles in human cancer progression. In the present study, we found miR-150 was overexpressed in gastric cancer cell lines and tissues. Ectopic expression of miR-150 promoted tumorigenesis and proliferation of gastric cancer cells. Luciferase reporter assay demonstrated that EGR2 was a direct target of miR-150. Collectively, our study demonstrated that overexpression of miR-150 in gastric cancer could promote proliferation and growth of cancer cells at least partially through directly targeting the tumor-suppressor EGR2, suggesting a potential strategy for the development of miRNA-based treatment of gastric cancer.
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                Author and article information

                Contributors
                Journal
                Biosci Rep
                Biosci. Rep
                bsr
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                30 September 2020
                10 September 2020
                : 40
                : 9
                : BSR20201337
                Affiliations
                [1 ]Breast thyroid surgery department, SSL Central Hospital of Dongguan City, Dongguan 523326, Guangdong Province, China
                [2 ]Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
                [3 ]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
                [4 ]Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510000, Guangdong Province, China
                [5 ]Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
                Author notes
                Correspondence: Siyuan Lin ( dgsyrjwk2015@ 123456126.com ) or Lihua Zhang ( dgsyrjwk@ 123456126.com )
                [*]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-2548-6831
                Article
                BSR20201337
                10.1042/BSR20201337
                7494982
                32840296
                adb1c30e-aff5-4e97-a959-f392ef73d709
                © 2020 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 23 April 2020
                : 01 August 2020
                : 19 August 2020
                : 25 August 2020
                Page count
                Pages: 10
                Categories
                Cancer
                Research Articles

                Life sciences
                breast cancer,foxo3,mir-940
                Life sciences
                breast cancer, foxo3, mir-940

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