Project description:There is increasing evidence that cancer recurrence and resistance to chemotherapy are linked to a subset of cancer stem cells. However, detecting these cells specifically and targeting them therapeutically remain challenging. As microRNAs (miRNAs) are emerging as key players in cancer biology, we set up to identify miRNAs involved in chemoresistance of breast cancer stem cells. In this study, we enriched populations of chemoresistant cancer stem cells from breast cancer and non-transformed breast cell lines using mammospheres. These mammospheres were treated or not with two chemoreagents, and we profiled surviving cells using miRNA microarray analysis. Comparison of the profiles from treated and untreated mammospheres as well as control and cancer cells yielded a six-miRNAs signature specific for chemoresistant stem cell-enriched subpopulations. From this signature miR-363-3p was found to be most highly overexpressed in various breast cancer cell lines and derived cancer stem cell-enriched populations, whereas non-tumorigenic cells had low levels. Inhibition of miR-363-3p was found to decrease cancer stem cell maintenance and tumorigenicity in vitro. Consistently, miR-363-3p downregulation decreased tumor growth and metastatization by human tumor cells transplanted in mice. Finally, miR363-3p levels in the sera of 38 breast cancer patients enrolled in a neoadjuvant trial correlated well with the response to the chemotherapeutic treatments. Altogether, miR363-3p was identified as a mediator of the breast cancer stem cell phenotype, and it may provide a predictor of the response to chemotherapy from a simple blood test, as well as a potential therapeutic approach for cancer stem cell targeting. This data set aims at identifying differentially expressed miRNAs in chemoresistant mammospheres, by the profiling of miRNA in MCF7 breast cancer cell-derived mammospheres selected to be resistant to 5 Fluorouracil (5FU) or Paclitaxel, as compared to unselected MCF7 mammospheres.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Chemoresistance remains a major obstacle to the successful treatment of breast cancer. Especially, more than 80% of cases cannot achieve pathological complete response (pCR) in patients who received neoadjuvant chemotherapy (NAC). Understanding the mechanisms involved in chemoresistance can guide the development of efficient therapies in patients with breast cancer. Herein, we identified a novel p62 isoform with a short 3′UTR (p62-SU, 662-nt) that is associated with chemoresistance by RNA-sequence and verified by qRT-PCR, 3′RACE, and northern blot in breast cancer cells and tissue specimens. Furthermore, enforced expression of p62-SU dramatically promoted the ability of proliferation, migration, invasion, and chemoresistance compared with p62 isoform with a long/full-length 3′UTR (p62-LU, 1485-nt) in vivo and in vitro. Mechanistically, we revealed that CPSF1 could regulate the 3′UTR shorting of p62 by alternative polyadenylation and then enhanced chemoresistance in breast cancer cells. In addition, we found that p62-SU escaped the repression of miR-124-3p and promoted the ability of p62-SU to produce more protein and, subsequently, p62-dependent chemoresistance. Together, our data suggest the p62-SU, generated by CPSF1, plays an essential role in the regulation of breast cancer chemoresistance through CPSF1-p62-miR-124-3p signaling.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.