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 ... -  《-》

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 ... -  《-》

LncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-related pathway regulates the doxorubicin resistance of prostate cancer DU-145 cells.

Our study aimed to investigate the effects of lncRNA LOXL1-AS1/miR-let-7a-5p/EGFR-axis on prostate cancer (PCa) progression. Microarray analysis was conducted to determine differentially expressed lncRNAs and mRNAs. Gene Set Enrichment analysis was implemented for verification of dys-regulated signaling pathways between DU-145 cells and doxorubicin-resistant prostate cancer DU-145 cells. Relative expression of lncRNA LOXL1-AS1 in doxorubicin-resistant prostate cancer DU-145 cells was analyzed by qRT-PCR. CCK-8 assay and flow cytometry analysis were employed to detect cell proliferation and apoptosis, respectively. Cell migration was performed by transwell assay. Furthermore, targeted relationships between lncRNA LOXL1-AS1 and miR-let-7a-5p, as well as miR-let-7a-5p and EGFR were predicted using bioinformatics analysis and validated by dual-luciferase reporter gene assay. Besides, tumor xenograft assay was utilized for verification of the roles of LOXL1-AS1 in PCa progression in vivo. Microarray analysis showed that lncRNA LOXL1-AS1 and EGFR were both downregulated, while miR-let-7a-5p was upregulated in doxorubicin-resistant prostate cancer DU-145 cells. MiR-let-7a-5p could target both lncRNA LOXL1-AS1 and EGFR to affect PCa progression. Upregulation of lncRNA LOXL1-AS1 promoted cell proliferation and migration, while suppressed cell apoptosis. Besides, it was further confirmed that EGFR was downregulated in drug-resistant PCa cells and negatively correlated with miR-let-7a-5p. Tumor xenograft assay verified that silence of lncRNA LOXL1-AS1 inhibited the tumor growth in vivo in DU-145 cells. Our results demonstrated that the lncRNALOXL1-AS1/miR-let-7a-5p/EGFR axis significantly affected proliferation, migration, and apoptosis of drug-resistant DU-145 Cells, which may provide us with a potential treatment strategy for drug-resistant PCa patients. © 2019 IUBMB Life, 2019.

Bai T ，Liu Y ，Li B 《-》

LncRNA DSCAM-AS1 promotes non-small cell lung cancer progression via regulating miR-577/HMGB1 axis.

Qiu Z ，Pan XX ，You DY 《-》

Silencing long non-coding RNA HNF1A-AS1 inhibits growth and resistance to TAM of breast cancer cells via the microRNA-363/SERTAD3 axis.

Li Y ，Liu L ，Lv Y ，Zhang Y ，Zhang L ，Yu H ，Tian W ，Zhang Z ，Cui S ... -  《-》