Breast Cancer Cell Colony Formation Research Articles

RETRACTED ARTICLE: LncRNA BCAR4 promotes migration, invasion, and chemo-resistance by inhibiting miR-644a in breast cancer

BackgroundMetastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression. MethodsThe RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell viability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo. ResultsLncRNA BCAR4 was significantly increased in breast cancer patients’ tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer.ConclusionsOur findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.

LncRNA LINC00668 promotes the progression of breast cancer by inhibiting apoptosis and accelerating cell cycle.

Objective: To elucidate how lncRNA 00668 (LINC00668) influences the development of breast cancer (BC).Materials and methods: Genome-wide expression profile of BC and paracancerous tissues were downloaded from The Cancer Genome Atlas (TCGA) and BC tissues and paracancerous tissues enrolled from our hospital for analyzing the expression level of LINC00668 and its correlation with prognosis. GSEA was conducted to analyze the potential functions of LINC00668. By transfection of sh-LINC00668 in BC cells, proliferation, apoptosis, cell cycle and colony formation of BC cells were accessed. Western blot was conducted to detect protein expressions of Ki-67, CDK4, Bcl-2, p21 and genes in AKT/mTOR pathways after LINC00668 knockdown in BC cells. Finally, tumor-bearing nude mice were administrated with BC cells. We compared the proliferative rate in mice with different administrations. Immunohistochemistry was carried out to access expression levels of Ki-67, CDK4, Bcl-2 and P21 in mice.Results: Both TCGA data and BC tissues harvested from our hospital indicated the higher expression of LINC00668 in BC tissues. LINC00668 expression was negatively correlated to prognosis of BC patients. GSEA pointed out that LINC00668 is enriched in regulations of cell cycle and apoptosis. By transfection of sh-LINC00668 in MDA-MB-231 and MDA-MB-436 cells, the proliferative and colony formation abilities of BC cells decreased. Besides, LINC00668 knockdown in BC cells induced apoptosis and arrested cell cycle. LINC00668 knockdown downregulated Ki-67, CDK4 and Bcl-2, but upregulated p21. The AKT/mTOR pathway was inhibited after LINC00668 silenced. In vivo experiments demonstrated the decreased proliferative rate in tumor-bearing mice administrated with sh-LINC00668 transfected BC cells. Consistently, immunohistochemical results showed lower positive expressions of Ki-67, CDK4 and Bcl-2, but higher positive expression of p21 in sh-LINC00668 group.Conclusion: LINC00668 is highly expressed in BC tissues and can promote the progression of BC by inhibiting apoptosis and accelerating cell cycle progression.

ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis.

Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice. The ZMYND8's oncogenic effect in breast cancer requires HIF-1 and HIF-2. We further showed that ZMYND8 interacts with HIF-1α and HIF-2α and enhances elongation of the global HIF-induced oncogenic genes by increasing recruitment of BRD4 and subsequent release of paused RNA polymerase II in breast cancer cells. ZMYND8 acetylation at lysines 1007 and 1034 by p300 is required for HIF activation and breast cancer progression and metastasis. These findings uncover a primary epigenetic mechanism of HIF activation and HIF-mediated breast cancer progression, and discover a possible molecular target for the diagnosis and treatment of breast cancer.

Ginsenoside Rp1 from Panax ginseng Exhibits Anti-cancer Activity by Down-regulation of the IGF-1R/Akt Pathway in Breast Cancer Cells

Cancer prevention is effective and reduces health care costs because cancer is often a preventable disease that can be affected by lifestyle factors. Therefore, researchers are interested in discovering natural compounds that have anticancer activities, such as delaying the development of cancer and preventing its progression. One such natural agent is ginseng (Panax ginseng), which is traditionally used in some parts of the world as a popular remedy for various diseases including cancer. We hypothesized that the ginsenoside Rp1, a component of ginseng, reduces cancer cell proliferation through inhibition of the insulin-like growth factor 1 receptor (IGF-1R)/Akt pathway. We first tested the efficacy of Rp1 against human breast cancer cell lines. Treatment with Rp1 inhibited breast cancer cell proliferation and inhibited both anchorage-dependent and -independent breast cancer cell colony formation. In addition, treatment with 20 μM Rp1 induced cycle arrest and apoptosis-mediated cell growth suppression. Our findings further indicated that Rp1 decreased the stability of the IGF-1R protein in breast cancer cells. Therefore, we suggest that Rp1 has potential as an anticancer drug and that IGF-1R is an important target for treatment and prevention of breast cancer.