Project description:Although many protein-coding genes have been identified to be aberrantly expressed in cervical cancer, the mechanisms of development and progression of cervical cancer remain unclear. In recent years, non-coding RNAs, especially including microRNAs and long non-coding RNAs, have been shown to play important regulatory roles in mammalian cell biology. In our study, we investigated the whole genome gene expression level changes by human transcriptome array in tumor tissues and paired adjacent non-tumor tissue of patients with cervical cancer. The functions of different expression microRNAs, long non-coding RNAs and mRNAs were further analyzed in vitro and in vivo using loss-of-function and gain-of-function approaches. A ten chip study using total RNA recovered from five separate cervical cancer tissues and five paired adjacent non-tumor samples.
Project description:The development of triple-negative breast cancers (TNBCs) – a subset of tumors with particularly aggressive pathogenesis – is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating a multitude of signaling nodes that propagate malignant traits in neighboring cancer cells. Characterization of these signaling cascades will better our understanding of TNBC biology, and stands to bring about novel therapeutics that can eliminate the morbidity and mortality associated with advanced disease. Here, we particularly focused on an emerging family of non-coding RNAs – called long non-coding RNAs or lncRNAs – and utilized a MSC-supported TNBC progression model to identify specific lncRNAs of functional relevance to TNBC pathogenesis. We used Affymetrix arrays to identify the gene expression changes that breast cancer cells (in this case, MDA-MB-231 cells) exhibit as they interact with admixed human MSCs
Project description:Although many protein-coding genes have been identified to be aberrantly expressed in cervical cancer, the mechanisms of development and progression of cervical cancer remain unclear. In recent years, non-coding RNAs, especially including microRNAs and long non-coding RNAs, have been shown to play important regulatory roles in mammalian cell biology. In our study, we investigated the whole genome gene expression level changes by human transcriptome array in tumor tissues and paired adjacent non-tumor tissue of patients with cervical cancer. The functions of different expression microRNAs, long non-coding RNAs and mRNAs were further analyzed in vitro and in vivo using loss-of-function and gain-of-function approaches.
Project description:To identify the mRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) involved in the pathogenesis of breast cancer, we performed the whole transcriptome sequencing. The whole transcriptome sequencing was performed with three breast cancer tissues with or without lymph node metastasis in each group, respectively. The results showed that 728 mRNAs, 131 lncRNAs, and 144 circRNAs were differentially expressed in lymph node metastasis group and no lymph node metastasis group (fold change≥2, p<0.05). These data indicate that dysregulation of mRNAs, lncRNAs, and circRNAs may contribute to breast cancer progression.
Project description:Long non-coding Rnas (lncRNAs) can act as oncogenes or tumor suppressors to regulate cancer development. We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with the prognosis of patients. Lentiviral vectors were used to overexpress CYP1B1-AS1 in MCF7 cells, and the target proteins bound to CYP1B1-AS1 were detected by pulldown assay and mass spectrometry. The function of CYP1B1-AS1 is unknown. Our study revealed the molecular mechanism of CYP1B1-AS1 inhibiting breast cancer proliferation in breast cancer, and provided a new strategy for the treatment of breast cancer targeting lncRNA.
Project description:Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, estrogen (E2 or 17b-estradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite intensive studies on estrogen-regulated coding genes over the past decades, molecular mechanisms underlying estrogen-regulated non-coding RNAs in breast cancer remain to be elucidated. Here, we performed extensive epigenomic studies including GRO-seq and ATAC-seq, and identified genome-wide estrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of estrogen-regulated lncRNAs correlates with the activation status of ERα-bound enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighboring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers.
Project description:Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, estrogen (E2 or 17b-estradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite intensive studies on estrogen-regulated coding genes over the past decades, molecular mechanisms underlying estrogen-regulated non-coding RNAs in breast cancer remain to be elucidated. Here, we performed extensive epigenomic studies including GRO-seq and ATAC-seq, and identified genome-wide estrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of estrogen-regulated lncRNAs correlates with the activation status of ERα-bound enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighboring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the estrogen-regulated LINC00160 and its neighboring RUNX1 might represent potential biomarkers for ER+ breast cancers.
Project description:Long non-coding RNAs (lncRNAs) are involved in cancer progression. In this study, the lncRNA profiling were analyzed in chemoresistant and sensitive breast cancer cells. We found a group of dysregulated lncRNAs in chemoresistant cells. Expression of dysregulated lncRNAs are correlated with dysregulated mRNAs, and enriched in GO and KEGG pathways related with cancer progression and chemoresistance development. Within those lncRNA-mRNA interactions, some lncRNAs may cis-regulate neighboring protein coding genes and involved in chemoresistance. The lncRNA NONHSAT028712 was then validated to regulate nearby CDK2 and interfere with cell cycle and chemoresistance. Furthermore, we identified another group of lncRNAs trans-regulated gene expression via interacting with different transcription factors (TF). Whereby NONHSAT057282 and NONHSAG023333 was found to modulate chemoresistance and most likely interacted with ELF1 and E2F1 respectively. In conclusion, this study reported for the first time the lncRNA expression patterns in chemoresistant breast cancer cells, and provided a group of novel lncRNA targets in mediating chemoresistance development in both cis- and trans- action mode. MCF-7/ADM replication 3 times, MCF-7/WT replication 3 times