M6A methylome in JQ1 treatment and control in MDA-MB-231 cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE219190 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:We report the application of MeRIP sequencing technology for high-throughput profiling of m6A methylome in breast cancer cells. Comparison of m6A methylome between METTL3-WT and METTL3-K177Q reconstituting cells revealed the following findings: 1) Significant global alteration of methylation sites due to K177Q mutation (termed as KQ-m6A signature). 2) GO analysis of the differential m6A-MeRIP candidates enriched pathways involved in chromatin modification, RNA splicing, DNA damage, cell cycle, and autophagy, consistent with a critical role of m6A-mediated nuclear biological activities and highlighted generally recognized cellular events associated with tumorigenesis. 3) we dissected potential mechanistic clues explaining the attenuated invasive phenotype in METTL3K177Q reconstituting cells.
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Project description:m6A methylome in JQ1 treatment and control in MDA-MB-231 cells.
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Project description:In the past decades, altered Follistatin‑like 1 (FSTL1) expression has been documented in a variety of cancers, while its functional roles are poorly understood. Particularly in breast cancer, the expression of FSTL1 and its signaling pathway remain to be determined. In the present study, an elevated FSTL1 expression and a supressed cell proliferation were detected in a specific brain metastatic cell line MDA‑MB‑231‑BR (231‑BR), compared with its parental cell line MDA‑MB‑231. However, this protein was hardly detected in the other three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1 specific shRNAs were used to overexpress or knock down FSTL1 in MDA‑MB‑231 or 231‑BR, respectively (MDA‑MB‑231FSTL1 or 231‑BRsh FSTL1). Results showed that overexpression of FSTL1 inhibited MDA‑MB‑231 cell proliferation, while knockdown of FSTL1 in 231‑BR cells promotes cell proliferation, compared with their corresponding control groups. These results were further confirmed in nude mouse xenografts. The tumor volume in 231‑BR cell-bearing mice was significantly smaller than that of MDA‑MB‑231 group, and reduction of tumor volume was detected in MDA‑MB‑231FSTL1 cell-bearing mice compared with the control group. Previous studies revealed that TGF‑β-Smad2/3 signaling pathway was activated in 231‑BR and MDA‑MB‑231FSTL1 cells, which may contribute to the inhibited cell proliferation. In addition, Smad3 knockdown could restore the inhibition of cell proliferation induced by FSTL1 overexpression in MDA‑MB‑231FSTL1 cells, indicating that the anti‑proliferative effect of FSTL1 overexpression may be associated with Smad3 involved TGF‑β signaling pathway regulation. This study identified FSTL1 as an inhibitor of cell proliferation in MDA‑MB‑231 and 231‑BR cell lines, which may provide new insights into the development and management of breast cancer.
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Project description:We report the application of immunoprecipitation of m6A methylated RNA followed by sequencing (MeRIP-Seq) in breast cancer MDA-MB-231 cells to identify PRMT5-mediated transcriptome-wide methylation patterns for doxorubicin response. Total RNAs from breast cancer cells were extracted with TRIzol. Then, mRNA sequencing and m6A sequencing were simultaneously performed. We find that doxorubicin induced the increasing m6A peaks compared to the control group, whereas inhibited by PRMT5. The transcripts exhibiting m6A methylation alteration by doxorubicin and PRMT5 were enriched for gene ontology (GO) terms related to DNA damage response and repair. The GO terms and KEGG annotations analysis identified BRCA1 signaling as being significantly altered through m6A methylation which induced by doxorubicin but inhibited by PRMT5. This study provides that PRMT5 promotes DNA damage repair through regulating m6A methylation of BRCA1 mRNA.
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Project description:m6A methylome in WT- and K177Q-METTL3 reconstituting MDA-MB-231 cells as well as in METTL3-deficient MDA-MB-231 cells.
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