Circular RNAs (circRNAs), a class of long-time-ignored noncoding RNA, have been revealed as multifunctional RNAs in recent years. However, the diagnostic values and the mechanism of most circRNAs in hepatocellular carcinoma (HCC) remain unknown. In this study, we revealed that the expression level of hsa_circ_0005986 in HCC was significantly lower than that in adjacent non-tumorous tissues (P < 0.001). Its levels in HCC cell lines, HepG2, SMMC7721, Huh7, MHCC97L, MHCC97H, and HCCLM3 were significantly lower than those in human normal hepatic cell line L02 (P < 0.001). In addition, the low expression level of hsa_circ_0005986 was correlated with chronic hepatitis B family history (P = 0.001), tumor diameters (P < 0.001), microvascular invasion (P = 0.026), and Barcelona Clinic Liver Cancer (BCLC) stage (P < 0.001). Further experiments demonstrated that both hsa_circ_0005986 and Notch1mRNA were targets of miR-129-5p, and that hsa_circ_0005986 downregulation liberated miR-129-5p and decreased the expression level of Notch1mRNA. More importantly, hsa_circ_0005986 downregulation accelerated cell proliferation by promoting the G0/G1 to S phase transition. We conclude that hsa_circ_0005986 function as microRNA sponge in tumorigenesis and can be used as a novel biomarker for HCC.

B-cell maturation antigen-targeted chimeric antigen receptor T cell therapy (BCMA CAR-T) is an effective treatment for relapsed refractory multiple myeloma (RRMM). However the pattern of infectious complications is not well-elucidated. We performed a single-center retrospective analysis of infection outcomes up to 1-year post BCMA CAR-T for MM from 2018-2020. Fifty-five MM patients were treated with BCMA CAR-T. Prior to lymphodepletion (LD), 35% of patients had severe hypogammaglobulinemia and 18% had severe lymphopenia. Most patients (68%) received bridging chemotherapy (BC) prior to LD. In the first month post CAR-T, 98% patients had grade 3-4 neutropenia. At 1-year post infusion, 76% patients had hypogammaglobulinemia. With a median follow-up of 6.0 months (95% CI: 4.7 to 7.4), there were a total of 47 infection events in 29 (53%) patients, 40% bacterial, 53% viral and 6% fungal. Most (92%) were mild-moderate and of the lower/upper respiratory tract system (68%). Half of infections (53%) occurred in the first 100 days post CAR-T infusion. Though no statistically significant risk factors for infection were identified, prior lines of therapy, use of BC, recent infections, and post CAR-T lymphopenia were identified as possible risk factors that need to be further explored. This is the largest study to date to assess the infectious complications post BCMA CAR-T. Despite multiple risk factors for severe immunosuppression in this cohort, relatively few life-threatening or severe infections occurred. Further larger studies are needed to better characterize the risk factors for and occurrence of infections post BCMA CAR-T.

These results indicated that hsa_circ_0003570 expression levels were associated with HCC clinicopathological characteristics.