Dataset Information

LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2.

ABSTRACT: Mounting evidence highlights long non-coding RNAs (lncRNAs) as crucial regulators in multiple types of biological processes and contributing to tumourigenesis. LINC01133, located in chromosome 1q23.2, was a recently identified novel lncRNA with a length of 1154nt. It was involved in the development of colorectal cancer and non-small cell lung cancer. However, its clinical relevance, biological functions and potential molecular mechanism in breast cancer are still unclear. In this study, we found that the LINC01133 expression was significantly down-regulated in breast cancer samples and was associated with progression and poor prognosis of breast cancer. Further experiments demonstrated that overexpression of LINC01133 inhibited invasion and metastasis in breast cancer both in vitro and in vivo. Mechanistic investigations revealed that LINC01133 repressed SOX4 expression by recruiting EZH2 to SOX4 promoter. Moreover, rescue experiments further confirmed that LINC01133 functional acted as an anti-oncogene, at least partly, via repressing SOX4 in breast cancer. Taken together, these findings imply that LINC01133 could serve as a novel prognostic biomarker and potential therapeutic target for breast cancer.

SUBMITTER: Song Z

PROVIDER: S-EPMC6815803 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2.

Song Zhiwang Z Zhang Xia X Lin Yun Y Wei Youzhen Y Liang Shujing S Dong Chunyan C

Journal of cellular and molecular medicine 20190926 11

Mounting evidence highlights long non-coding RNAs (lncRNAs) as crucial regulators in multiple types of biological processes and contributing to tumourigenesis. LINC01133, located in chromosome 1q23.2, was a recently identified novel lncRNA with a length of 1154nt. It was involved in the development of colorectal cancer and non-small cell lung cancer. However, its clinical relevance, biological functions and potential molecular mechanism in breast cancer are still unclear. In this study, we found ...[more]

PMID: 31557401

Similar Datasets

Project description:ObjectiveTo investigate the effects of miR-300 and PTTG1 on osteosarcoma invasion and metastasis and explore the molecular mechanism of osteosarcoma invasion and metastasis.ObjectiveWestern blot was used to detect the expression of PTTG1 in human osteoblasts hFOB1.19 and osteosarcoma cell MG63 and to detect the transfection efficiency of cells transfected with PTTG1-knockdown plasmid; Transwell invasion assay and CCK8 assay detected the effects of knockdown of PTTG1 and overexpression of miR-300 on the invasion and proliferation of osteosarcoma cell MG63. On-line prediction and screening of microRNAs (miRNAs) with complementary PTTG1 binding was conducted. qRT-PCR was performed to examine the expression of miR-300 in hFOB1.19 and MG63 cells, and Western blotting was used to detect the expression of PTTG1 in MG63 cells after transfection with a miR- 300 plasmid. Double luciferase assay was used to detect the targeted binding of miR-300 and PTTG, Transwell invasion assay and CCK8 assay were used to detect the effects of overexpression of miR-300 and overexpression of PTTG1 plasmid on invasion and proliferation of osteosarcoma cell line MG63.ObjectivePTTG1 was highly expressed in MG63 cells (P=0.0002). PTTG1 knockdown significantly inhibited the invasion (P=0.0002) and proliferation (P=0.0039) of MG63 cells. Based on the results of online prediction of complementary miRNAs to PTTG1 and analysis of the data from NCBI database, miR-300 was determined as the target miRNA in this study. qRT-PCR results showed a significantly decreased expression of miR-300 in MG63 cells (P=0.0004). Overexpression of MiR-300 in MG63 cells significantly decreased the expression of PTTG1 (P=0.0007), and the expressions of miR-300 and PTTG1 were negatively correlated. Dual luciferase assay showed that miR-300 could specifically bind to PTTG1 (P=0.001). Overexpression of PTTG1 could significantly reverse the effect of miR-300 overexpression on invasion (P=0.0003) and proliferation (P=0.0077) of MG63 cells.ObjectiveOverexpression of miR-300 can inhibit the invasion and metastasis of osteosarcoma cell MG63 by targeting PTTG1.

Project description:BACKGROUND:BRD7 is a tumor suppressor known to inhibit cell proliferation and cell cycle progression and initiate apoptosis in breast cancer. However, the function and underlying molecular events of BRD7 in tumor invasion and metastasis in breast cancer are not fully understood. METHODS:BRD7 expression was assessed in two stable cell lines MDA231 and MCF7 with BRD7 overexpression and one stable cell line MDA231 with BRD7 interference using qRT-PCR and western blotting. CCK8 assay was used to examine the proliferation ability of MDA231 and MCF7 cells. Scratch wound healing assay was used to evaluate cell migration in MDA231 and MCF7 cells. Both Matrigel and three-dimensional invasion assays were performed to investigate the cell invasion ability after BRD7 overexpression or silencing or YB1 restoration in MDA231 and MCF7 cells. The potential interacting proteins of BRD7 were screened using co-immunoprecipitation combined with mass spectrometry and verified by co-immunoprecipitation in HEK293T cells. Additionally, we confirmed the specific binding region between BRD7 and YB1 in HEK293T cells by constructing a series of deletion mutants of BRD7 and YB1 respectively. Finally, xenograft and metastatic mouse models using MDA231 cells were established to confirm the effect of BRD7 on tumor growth and metastasis. RESULTS:Here, the results of a series of assays in vitro indicated that BRD7 has the ability to inhibit the mobility, migration and invasion of breast cancer cells. In addition, YB1 was identified as a novel interacting protein of BRD7, and BRD7 was found to associate with the C-terminus of YB1 via its N-terminus. BRD7 decreases the expression of YB1 through negatively regulating YB1 phosphorylation at Ser102, thereby promoting its proteasomal degradation. Furthermore, gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT) is the common change occurring with altered expression of either BRD7 or YB1 and that BRD7 represses mesenchymal genes and activates epithelial genes. Moreover, restoring the expression of YB1 antagonized the inhibitory effect of BRD7 on tumorigenicity, EMT, invasiveness and metastasis through a series of in vitro and in vivo experiments. Additionally, BRD7 expression was negatively correlated with the level of YB1 in breast cancer patients. The combination of low BRD7 and high YB1 expression was significantly associated with poor prognosis, distant metastasis and advanced TNM stage. CONCLUSIONS:Collectively, these findings uncover that BRD7 blocks tumor growth, migration and metastasis by negatively regulating YB1-induced EMT, providing new insights into the mechanism by which BRD7 contributes to the progression and metastasis of breast cancer.

Project description:PurposeIncreasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo.MethodsWe used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging.ResultsSOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel.ConclusionsSOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.

Dataset Information

LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2.

Publications

LINC01133 inhibits breast cancer invasion and metastasis by negatively regulating SOX4 expression through EZH2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets