The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer.

Background: Huangci Granule is a traditional Chinese medicine for treating metastatic colorectal cancer (mCRC). Objective: To evaluate the efficacy and safety of Huangci Granule combination with chemotherapy and cetuximab (CET) or bevacizumab (BV) for treating mCRC. Methods: We performed a randomized, controlled, and double-blind trial and recruited patients with mCRC who were planned to undergo chemotherapy combined with CET or BV. The treatment group was treated with Huangci Granule, while the control group was treated with placebo. Continuous treatment until disease progression, death, intolerable toxicity or up to 6 months. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was quality of life and safety. Result: 320 patients were randomly assigned to receive treatment, including 200 first-line patients and 120 second-line patients. In the first-line treatment, the median PFS was 9.59 months (95% CI, 6.94-13.25) vs 6.89 months (95% CI, 4.99-9.52) in treatment group and control group (HR, 0.69; 95% CI, 0.50-0.97; P = 0.027). Chinese medicine was an independent factor affecting the PFS. In the second-line treatment, the median PFS was 6.51 months (95% CI, 4.49-9.44) vs 4.53 months (95% CI, 3.12-6.57) in the treatment group and control group (HR, 0.65; 95% CI, 0.45-0.95; P = 0.020). Compared with the control group, "role function," "social function," "fatigue," and "appetite loss" were

Background: Multiple studies have reported that the immune system is under the control of a circadian clock, especially in cancers, but how circadian clock genes shape tumor immune cell infiltration in hepatocellular carcinoma (HCC) remains unclear. Methods: The rhythmicity of circadian clock genes was investigated using the GETx database. The expression and methylation level of circadian clock genes in HCC and paracancerous was evaluated using the GETx and TCGA databases. The differential expression of circadian clock genes in HCC was analyzed using the “limma” package of the R 4.0.4 software. The prognosis of each circadian clock gene was accessed by Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. Quantitative real-time PCR and immunohistochemistry (IHC) was carried out to confirm the results. The relationship between circadian rhythm and immune infiltration in HCC was evaluated using the TIMER database and the CIBERSORT algorithm. Results: In addition to RORA, RORB, and ARNTL2, there was a rhythmic expression of other circadian clock genes in liver tissue. The correlation between the expression of circadian clock genes differed when comparing HCC and liver tissue. HCC patients who express low levels of PER-1and CRY2 had a poor overall survival (OS). In contrast, patients with higher expression of NPAS2 had a poor prognosis. In HCC, the expression of the PER-1, CRY2, and NPAS2 genes was closely related to immune infiltration. Conclusion: Our study indicated the disruption of the expression of circadian clock-regulated genes in HCC and identified PER-1, CRY2, and NPAS2 as independent predictors of survival. These genes may be applied as candidate molecular targets for diagnosis and therapy of HCC.

LncRNA plays a pivotal role in the stemness and drug resistance of lung cancer. Here, we found that lncRNA-AC026356.1 was upregulated in stem spheres and chemo-resistant lung cancer cells. Our fish assay also shows that AC026356.1 was predominantly located in the cytoplasm of lung cancer cells and does not have protein-coding potential. Silencing AC026356.1 significantly inhibited proliferation and migration but increased apoptosis in A549-cisplatin (DDP) cells. Additionally, IGF2BP2 and the lncRNA-AC026356.1 positively regulated the proliferation and stemness of stem-like lung cancer cells. Further mechanistic investigation revealed that METTL14/IGF2BP2-mediated m6A modification and stabilization of the AC026356.1 RNA. Functional analysis corroborated that AC026356.1 acted as a downstream target of METTL14/IGF2BP2 and AC026356.1 silencing could block the oncogenicity of lung cancer stem-like cells. AC026356.1 expression was correlated with immune cell infiltration and T cell exhaustion. Compared with paired adjacent normal tissues, lung cancer specimens exhibited consistently upregulated METTL14/IGF2BP2/AC026356.1. M6A-modified METTL14/IGF2BP2/AC026356.1 loop may serve as a potential therapeutic target and prognostic predictor for lung cancer therapy and diagnosis in the clinic.

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