Circadian rhythm regulates the function of immune cells and participates in the development of tumors.

Circadian rhythms are present in almost all cells and play a crucial role in regulating various biological processes. Maintaining a stable circadian rhythm is essential for overall health. Disruption of this rhythm can alter the expression of clock genes and cancer-related genes, and affect many metabolic pathways and factors, thereby affecting the function of the immune system and contributing to the occurrence and progression of tumors. This paper aims to elucidate the regulatory effects of BMAL1, clock and other clock genes on immune cells, and reveal the molecular mechanism of circadian rhythm's involvement in tumor and its microenvironment regulation. A deeper understanding of circadian rhythms has the potential to provide new strategies for the treatment of cancer and other immune-related diseases.

A Novel ER Stress Mediator TMTC3 Promotes Squamous Cell Carcinoma Progression by Activating GRP78/PERK Signaling Pathway.

During tumor progression, tumor cells are exposed to various stress conditions, which result in endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) to restore ER homeostasis. Accumulating evidence reported the orchestrating role of ER stress in epithelial-mesenchymal transition (EMT) progress, but the detailed mechanism was unclear. Here, we identified ectopic expression of TMTC3 in cells undergoing ER stress and verified the association with EMT markers through the cellular model of ER stress and database analysis. TMTC3 was abnormally highly expressed in squamous cell carcinomas (SCCs), and regulated by TP63, an SCCs-specific transcription factor. Biological function experiments indicated that TMTC3 promoted a malignant phenotype in vitro, and accelerated tumor growth and metastasis in vivo. RNA-seq analyses and further experiments revealed that TMTC3 promoted the expression of EMT markers via interleukin-like EMT inducer (ILEI, FAM3C). Further studies on the mechanism showed that TMTC3 disrupted the interaction between PERK and GRP78 to activate the PERK pathway and promote the nuclear translocation of ATF4, which increased the transcriptional activity of ILEI. These findings indicated that TMTC3 activates GRP78/PERK signaling pathway during ER stress-induced EMT, which might serve as a potential therapeutic target in SCCs.

miR-4306 Suppresses Proliferation of Esophageal Squamous Cell Carcinoma Cell by Targeting SIX3.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and the primary cause of cancer-related mortality in China. micoRNA plays a vital role during tumor initiation and malignant progression. miR-4306 has been reported to negatively regulate aggressive cell phenotypes in triple-negative breast cancer (TNBC). Nevertheless, the function of miR-4306 in ESCC was still not clear. In this study, we detected miR-4306 expression by quantitative real-time reverse transcription-PCR (qRT-PCR) and found that miR-4306 expression was downregulated in human ESCC tissue samples and cell lines. Moreover, miR-4306 overexpression could restrain ESCC cell proliferation, migratory and invasive ability and epithelial-mesenchymal transition (EMT), promote cell apoptosis after treatment with or without cisplatin. In contrast, inhibiting the expression of miR-4306 showed the opposing results. Furthermore, we explored the molecular mechanism of effects of miR-4306 and found that miR-4306 inhibited the expression of SIX3 by interaction with SIX3 3'UTR in ESCC cells, and SIX3 overexpression significantly reversed the effect of miR-4306-mediated ESCC cells proliferation. The current study provided evidence of miR-4306 as a tumor suppression gene in ESCC.

Aurora kinase inhibitor VX­680 suppresses the proliferation and migration of HUVECs and angiogenesis.

Angiogenesis serves a key role in tumor growth and metastasis. VX­680, a potent inhibitor targeting the Aurora kinase family, is widely used in the inhibition of tumor progression. However, the effect of VX­680 on angiogenesis remains unknown. The present study identified that VX­680 inhibited human umbilical vein endothelial cell (HUVEC) proliferation and promoted HUVEC apoptosis by inducing the cleavage of PARP and caspase­3. VX­680 also markedly decreased the migration and tube formation of HUVECs in a dose­dependent manner. In addition, VX­680 significantly suppressed the formation of blood vessels in a dose­dependent manner confirmed by a chicken embryo chorioallantoic membrane assay in vivo. Furthermore, VX­680 inhibited the expression levels of vascular endothelial growth factor and phosphorylated RAC­α serine/threonine­protein kinase in HUVECs. These results suggested that VX­680 suppressed angiogenesis and may be a potential novel anti­angiogenic agent.

Light regulation to chlorophyll synthesis and plastid development of the chlorophyll-less golden-leaf privet.

Ligustrum vicaryi L. is a hybrid of Ligustrum ovalifolium Hassk. var. aureo-marginatum and Ligustrum vulgale L., and displays a chlorophyll-less phenotype. Therefore it is widely used as a horticultural shrub because of its golden-color leaves. Its putative mechanism, light responses, chlorophyll synthesis and plastid development were studied. L. vicaryi has a higher level of 5-aminolevulinic acid (ALA), but lower levels of chlorophylls compared with L. quihoui. The yellowish phenotype of L. vicaryi upper leaves could be attributed to their hampered conversion from chlorophyllide into chlorophyll a. Despite the enhanced ALA level and the decreased thylakoid stacking in plastids, L. vicaryi golden leaves contain normal levels of Lhcb transcripts and photosystem apoproteins. Furthermore, reactive oxygen species (ROS) accumulation is almost the same in L. vicaryi and L. quihoui. The golden leaves often turn green and the contents of chlorophylls increase with decreasing light intensity. Dynamic changes of chlorophyll-synthesis-system under the light transition were also analyzed.