DSCAM-AS1 promotes tumor growth of breast cancer by reducing miR-204-5p and up-regulating RRM2.

Breast cancer (BC) is a common malignancy worldwide. More than 3 700 000 women die of BC every year. DSCAM-AS1 was overexpressed several kinds of cancer and miR-204-5p was lowly expressed, which indicated that miR-204-5p had anti-tumor activity and DSCAM-AS1 had pro-tumor activity. We intended to analyze DSCAM-AS1, miR-204-5p, and ribonucleotide reductase M2 (RRM2). Microarray analysis and quantitative Real Time fluorescence Polymerase Chain Reaction (qRT-PCR) were employed to determine DSCAM-AS1 and miR-204-5p expression. Luciferase reporter assay was applied to examine the target relationship between DSCAM-AS1, miR-204-5p, and RRM2. Cell Counting Kit-8 (CCK-8 assay), transwell assay, and flow cytometry were used to detect cell proliferation, invasion, and apoptosis. The expression of DSCAM-AS1, miR-204-5p, and RRM2 were confirmed by Western blot. We also conducted in vivo assay to verify the effect of DSCAM-AS1. DSCAM-AS1 was up-regulated, while miR-204-5p was down-regulated in BC tissues and cells. DSCAM-AS1 directly targeted miR-204-5p. DSCAM-AS1 promoted the proliferation and invasion of BC cells by reducing miR-204-5p and inhibiting miR-204-5p expression. DSCAM-AS1 expression was related to the expression of RRM2, and miR-204-5p could reverse the function of DSCAM-AS1. RRM2 was up-regulated in BC cells, and miR-204-5p inhibited RRM2 expression by targeting RRM2. Overexpression of RRM2 stimulated proliferation and cell invasion and impeded apoptosis. In vivo experiments showed that knockdown of DSCAM-AS1 decreased the tumorigenesis of BC cells, increased the expression of miR-204-5p. DSCAM-AS1 promoted proliferation and impaired apoptosis of BC cells by reducing miR-204-5p and enhancing RRM2 expression. DSCAM-AS1/miR-204-5p/RRM2 may serve as novel therapeutic targets for BC.

Liang WH ，Li N ，Yuan ZQ ，Qian XL ，Wang ZH ... -  《-》

Long intergenic non-protein coding RNA 1094 (LINC01094) promotes the progression of breast cancer (BC) by regulating the microRNA-340-5p (miR-340-5p)/E2F transcription factor 3 (E2F3) axis.

Wu X ，Kong C ，Wu Y 《-》

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression.

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.

Yan L ，Li K ，Feng Z ，Zhang Y ，Han R ，Ma J ，Zhang J ，Wu X ，Liu H ，Jiang Y ，Zhang Y ，Zhu Y ... -  《-》

LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer.

To investigate the influence of long noncoding RNA (lncRNA) DSCAM-AS1 on the propagation and apoptosis of Tamoxifen-resistant (TR) breast cancer cells via regulation of mircoRNA (miR)-137 and epidermal growth factor receptor pathway substrate 8 (EPS8). Data of GSE5840 downloaded from the Gene Expression Omnibus database were utilized to screen out aberrantly expressed lncRNA and messenger RNA in breast cancer tissue samples. The expressions of DSCAM-AS1, miR-137, and EPS8 were determined by quantitative real time polymerase chain reaction (qRT-PCR). Cell lines were screened by half maximal inhibitory concentration (IC 50 ). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and the flow cytometry assay were used to detect cell proliferation, apoptosis, and cell cycle. The relationship among DSCAM-AS1, miR-137, and EPS8 was studied by miRcode, TargetScan, and Pearson correlation coefficient. A xenograft mouse model experiment was performed to demonstrate the effect of DSCAM-AS1 and EPS8 on tumor growth in vivo. LncRNA DSCAM-AS1 and EPS8 were significantly upregulated, whereas miR-137 was downregulated in TR tissues. DSCAM-AS1 could promote the Tamoxifen resistance of breast cancer, and it was negatively correlated with miR-137, whereas positively correlated with the expression of EPS8 in TR breast cancer tissues. Furthermore, miR-137 could inhibit tumor development and arrest cell cycle at the G0/G1 phase by targeting the 3'-UTR of EPS8. DSCAM-AS1 targeted miR-137 and EPS8 to promote propagation of TR breast cancer cells and inhibit cell apoptosis. LncRNA DSCAM-AS1 acts as a competing endogenous RNA of miR-137 and regulates EPS8 to promote cell reproduction and suppresses cell apoptosis in TR breast cancer.

Ma Y ，Bu D ，Long J ，Chai W ，Dong J ... -  《-》

Knockdown of long noncoding RNA TP73-AS1 suppresses the malignant progression of breast cancer cells in vitro through targeting miRNA-125a-3p/metadherin axis.

TP73 antisense RNA 1 (TP73-AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73-AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis. Expression of TP63-AS1, miRNA-125a-3p (miR-125a) and metadherin (MTDH) was detected by real-time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK-8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo. Expression of TP73-AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC-70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N-cadherin and Vimentin level. Moreover, TP73-AS1 downregulation restrained the tumor growth of HCC-70 cells in vivo. Mechanically, TP73-AS1 functioned as a molecular "sponge" for miR-125a to modulate MTDH, a downstream target of miR-125a. Intriguingly, both miR-125a overexpression and MTDH silencing exerted a tumor-suppressive effect in the malignant progression of HCC-70 and MB231 cells, which was counteracted by TP73-AS1 upregulation and miR-125a downregulation, respectively. Knockdown of TP73-AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR-125a and upregulating MTDH, suggesting a novel TP73-AS1/miR-125a/MTDH pathway in the malignant progression of breast cancer.

Liu Y ，Wei G ，Ma Q ，Han Y ... -  《-》