Ontology highlight
ABSTRACT:
PROVIDER: PRJNA725393 | ENA |
REPOSITORIES: ENA
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Project description:Micro RNA (miRNA) profiling of breast cancer subtype was demonstrated using RT-PCR. We present herein two cases with miRNA profiling in estrogen receptor (ER)-positive and -negative breast cancer. The level of miR-181a expression in ER-positive cancer was higher than in ER-negative cancer, while expression of miR-27a, -107 and -195 was lower in ER-positive when compared with ER-negative cancer.
2018-10-13 | GSE121172 | GEO
Project description:Estrogen and estrogen receptor (ER) signaling play critical roles in the development of ER-positive breast cancer, and endocrine therapy is the frontline treatment for ER-positive breast cancer patients. However, the primary and acquired resistance to endocrine therapy including tamoxifen and fulvestrant remains as the major challenge in the clinic. Here, we identified an estrogen-induced lncRNA, LINC02568, through transcriptomic analysis, which is highly expressed in ER-positive breast cancer. LINC02568 is functional important in ER-positive breast cancer cell growth in vitro and tumorigenesis in vivo as well as endocrine therapy resistance. Mechanically, we demonstrated that LINC02568 regulates, in trans, estrogen/ERα-induced gene transcriptional activation by sponging miR-1233-5p to stabilize ESR1 mRNA in the cytoplasm. Meanwhile, LINC02568 contributes to tumor-specific pH homeostasis in breast cancer cells by regulating CA12 in cis in the nucleus. The dual functions of LINC02568 together contribute to breast cancer cell growth and tumorigenesis as well as endocrine therapy resistance. Antisense oligonucleotides (ASO) targeting LINC02568 significantly inhibits ER-positive breast cancer cell growth in vitro and tumorigenesis in vivo as well as resensitize tamoxifen-resistant cells to tamoxifen. Furthermore, combination treatment with ASO targeting LINC02568 and tamoxifen exhibits synergistic effect on tumor growth. Taken together, our findings revealed dual mechanisms of LINC02568 in regulating ERα signaling and pH homeostasis in ER-positive breast cancer, and indicated that targeting LINC02568 might represent a potential therapeutic avenue in clinic.
2023-09-13 | GSE217190 | GEO
Project description:CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
2019-03-04 | GSE117747 | GEO
Project description:CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
2019-03-04 | GSE117745 | GEO
Project description:Approximately 30% of cases are resistant to TAM, which has become a major obstacle for breast cancer therapy.In this study, we demonstrated that CUL4B promotes TAM resistance in breast cancer cells through miR-32-5p/ER-α36 axis. CUL4B is overexpressed in TAM-resistant breast cancer cells and positively correlates with the levels of ER-α36 protein in human breast cancer specimens. Mechanistically, CUL4B positively regulates ER-α36 expression by epigenetically repressing the transcription of miR-32-5p. These findings provide not only a mechanistic insight into the role of CUL4B in regulating TAM sensitivity but also a potential target for the therapy of breast cancer.
2022-09-08 | GSE158651 | GEO
Project description:CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
2019-03-04 | GSE117746 | GEO
Project description:CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
2019-03-04 | GSE117743 | GEO
Project description:CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor (ER)-positive breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after exposure to palbociclib in ER-positive breast cancer cells. Increased CDK6 in resistant cells was dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediated transfer of the resistance phenotype between neighboring cell populations. We confirmed these data in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating clinical relevance of this mechanism. Additionally, the CDK4/6 inhibitor resistance phenotype can be reversed in vitro and in vivo by a prolonged drug holiday.
2019-03-04 | GSE117742 | GEO
Project description:Poly (ADP-ribose) polymerase-1 (PARP-1), a multifunctional chromatin-modulating protein, has gained considerable attention as a target for therapeutic inhibitors in breast cancers. Accumulating evidence suggests a pathological role for PARP-1 in breast cancer through its effects on the transcription of tumor-related genes. Here we report the role of PARP-1 in estrogen-dependent transcription in estrogen receptor alpha (ERα)-positive breast cancers. Global nuclear run-on and sequencing (GRO-seq) analyses suggest that PARP-1 controls the expression of estrogen-regulated genes in ER-positive (ER+) MCF-7 breast cancer cells. Further, ChIP-seq analyses revealed that PARP-1 directly regulates the ligand-dependent binding of ERa and FoxA1 to a subset of its genomic binding sites. Finally, we uncovered that the expression levels of the PARP-1 and estrogen coregulated gene set are enriched in luminal molecular-subtype of breast tumors and high PARP-1 expression in ER+ cases correlates with poor survival. Additionally, treatment with PARP-1 selective inhibitors showed attenuated estrogen-dependent growth of ER+ breast cancer cells. Taken together, the current study suggests that PARP-1 regulates critical molecular pathways that underlie proliferation of ER+ breast cancer cells.
2021-10-13 | GSE166168 | GEO
Project description:We used a genome-wide approach (High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, or HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. Finally, we show that miRNA targets and networks defined by our analysis are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer.
2014-08-04 | GSE57855 | GEO