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Tuning circadian rhythm of CAFs against cancer progression

ABSTRACT: Tuning circadian rhythm of CAFs against cancer progression

PROVIDER: PRJNA1171862 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30954366_1.fastq.gz	Fastqsanger.gz
	SRR30954366_2.fastq.gz	Fastqsanger.gz
	SRR30954367_1.fastq.gz	Fastqsanger.gz
	SRR30954367_2.fastq.gz	Fastqsanger.gz
	SRR30954368_1.fastq.gz	Fastqsanger.gz

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Tuning circadian rhythm of CAFs against cancer progression

Project description:Circadian disruption orchestrates various biological functions associated with carcinogenesis and tumor progression in cancer cells. Yet the influential role in the tumor microenvironment (TME), including cancer-associated fibroblasts (CAFs), remains unveiled. Here, we report an uncovered signaling axis, BMAL1-LHX8, that elicits the transitioning of CAF-like properties via coordinating the tumor-supportive activity in ameloblastoma (AM) stromal. Both in the co-culture system and stroma-rich AM tumoroid model, CAFs augmented tumor growth, cell proliferation, and metabolic activities. Time-series RNA-sequencing analysis indicated the perturbation of circadian rhythm in the AM+CAF group and LHX8 was considerably involved. CRISPR/cas9 system-based loss-of-function study suggested that the BMAL1-LHX8 signaling axis was highly correlated with several tumor-supportive activities, including secretion of growth factors and ECM remodeling molecules. It also contributed to the resistance of BRAF inhibitor (PLX4032), which could be effectively suppressed by the clock regulator (GSK4112, an agonist of REV-ERB which suppresses BMAL1 expression). This phenomenon confirmed that GSK4112 elevated the anti-tumor efficacy of PLX4032 in the xenograft model. Collectively, these data underscore the role of the BMAL1-LHX8 axis in exacerbating the CAF-like transitioning in AM stromal and tuning the circadian rhythm via clock regulators. This research offering the experimental evidence for the development of chrono-chemotherapy and offering new possibilities for the cancer treatment in the future.

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Circadian rhythm in NIH3T3 cells

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Project description:Identification of cyclical expressed coding and non-coding genes during the circadian rhythm in NIH3T3 cells. NIH3T3 cells were synchronized for their circadian rhythm and RNA sequencing were performed at several time points along the rhythm. This data was used to identify cyclical expressed genes as well as long intergenic non-coding RNAs. NIH3T3 cells were synchronized with 100 nM Dexamethasone for 2 hours, then medium was changed to normal culture medium (0h). Every 4 hours cells were harvested, RNA isolated and RNAseq performed.

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Effect of d-alanine on circadian rhythm

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Project description:CIRCADIAN RHYTHM REPROGRAMMING DURING LUNG INFLAMMATION

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