Circadian clock gene BMAL1 inhibits the proliferation and tumor-formation ability of nasopharyngeal carcinoma cells and increases the sensitivity of radiotherapy

Jul 29, 2022Chronobiology international

The body’s clock gene BMAL1 slows growth and tumor formation in nasopharyngeal cancer cells and may make radiotherapy more effective

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Abstract

The mRNA expression levels of the circadian clock gene fluctuated rhythmically over 48 hours in nasopharyngeal carcinoma (NPC) cells.

Changes in the expression of the circadian clock gene were observed in both NPC and normal nasopharyngeal epithelial cells.
Overexpression of the circadian clock gene inhibited the proliferation of NPC cells, while its knockdown promoted proliferation.
In a xenograft model, upregulation of the circadian clock gene inhibited tumor growth and increased sensitivity of NPC cells to radiotherapy.
Downregulation of the circadian clock gene was associated with enhanced tumor growth and reduced radiosensitivity.
Gene Set Enrichment Analysis indicated that the circadian clock gene significantly impacted the p53 signaling pathway.

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is a core circadian clock gene that is expressed rhythmically in a variety of tumor cells and is related to cancer cell proliferation and chemoradiotherapy sensitivity. Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC). However, the rhythmicity ofin NPC, as well as its precise role in radiotherapy, remains unclear. We assessed changes inexpression over 48 h in NPC cells and normal nasopharyngeal epithelial cells NP69 using real-time quantitative polymerase chain reaction (RT-PCR) and western blotting (WB). Then, we induced the overexpression and knocked-down the levels ofin NPC cells, and subsequently used Cell Counting Kit-8 assays to assess the proliferation of NPC cells. Xenograft tumour growth was used to evaluate the effect ofin vivo. Immunohistochemical staining was used to detect the expression of BMAL1 protein in transplanted tumors. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological signaling pathway. Finally, RT-PCR and WB were used to detect the expressions ofand. The results showed that the mRNA expression levels of circadian clock genefluctuated rhythmically with time, and the expression levels ofalso changed depending on the protein levels in NPC and NP69 cells. Overexpression ofinhibited the proliferation of NPC cells, while knockdownhad the opposite effects. In a xenograft model, we observed that the upregulation ofinhibited tumor growth and enhanced the sensitivity of NPC cells to radiotherapy. Ultimately, the downregulation ofpromoted tumor growth and decreased radiosensitivity. GSEA analysis suggested thatsignificantly affected the p53 pathway. Overexpression ofpromoted the expression of p53 and p21, while the knockdown ofinhibited the expression of p53 and p21. We speculate thathas the potential to be a prognostic biomarker and therapeutic target for NPC. BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1, p53p21BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1BMAL1

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Circadian clock gene BMAL1 inhibits the proliferation and tumor-formation ability of nasopharyngeal carcinoma cells and increases the sensitivity of radiotherapy

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