Jie Chen, shanghai xuhui central hospital,2023.09.12

Description

OEP004528

Zhenhao Liu, Central South University,2021.01.08

Description

Exogenous glycine deprivation inhibits tumor progression in multiple myeloma (MM) both in vitro and in vivo. To explore the underlying mechanisms of glycine metabolisms in MM cells, RNA-sequencing was performed in ARP1 cells cultured in the absence or presence of glycine (10 mg/L) for 24 hours. Genes involving glycine metabolism, among which SLC6A9, GLDC, SHMT2, and GSS were significantly highly expressed. This finding indicated that exogenous glycine deprivation mainly affected glycine transport, glycine cleavage, the interconversion between glycine and serine, and glutathione synthesis. In addition, enrichment analysis of signaling pathways based on different genes showed half of top 10 enriched pathways were related to cell mitosis and DNA damage.

OEP001473

Xiaojuan Fan, ,2020.11.16

Description

Although most eukaryotic mRNAs require the 5’-cap for translation, some mRNAs can also be translated through a cap-independent pathway. Here we developed a cell-based system to unbiasedly screen human transcriptome for sequences that drive cap-independent circRNA translation, and identified >10,000 endogenous sequences. These sites were found in all mRNA regions, with features distinct from canonical IRESs, and thus were defined as Cap-independent Translation Initiation sites (CiTI). The CiTIs at 5’-UTR tend to pair with 18S rRNA to promote translation. However, the CiTIs at 3’-UTR may function either as IRESs to drive downstream ORF translation, or as translation enhancers to promote upstream main ORF translation by unwinding the highly structured 5’-UTR. We further identified trans-acting factors that specifically bind CiTIs at 3’-UTR to promote upstream ORF translation, including several components of translation initiation complexes such as DHX29. Knockdown of DHX29 reduced translation of a specific set of mRNAs, including HIF1A whose translation is enhanced by a 3’-CiTI during hypoxia. Consistently, deletion of this 3’-CiTI from HIF1A can suppress neuroblastoma cell proliferation in vitro and in vivo. Collectively, the identification and study of CiTI revealed new diversity in translational regulation that may play key roles in mRNA translation during stress response.

OEP001285

Zhenhao Liu, SCBIT,2018.01.18

Description

Primary liver cancer (PLC) is the third largest contributor to cancer mortality in the world. PLC is a heterogeneous disease that encompasses several biologically distinct subtypes including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). CHC is a distinct, albeit rare, subtype of PLC and is comprised of cells with histopathological features of both HCC and ICC. Several studies have focused on the mutation and expression landscapes of HCC and ICC. However studies of CHC were rare. The aim of the current study was to identify genetic and gene expression alterations in the carcinogenesis and development of CHC and ICC in the Chinese population. Unraveling both similar and differing patterns among these subtypes may help to identify personalized medicine approaches that could improve patient survival.

Used ID

NODEP00371762  

OEP000118

Jianxiang Shi, Zhengzhou University,2023.05.25

Description

Background BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells. Methods This study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis. Results We compared the heterogeneity of CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT+NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1βhi Mφ, S100A9hi Mφ, interferon-responsive Mφ, CD16hi Mφ, MARCO hi Mφ, and S100A11hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell–cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy. Conclusion Taken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.

OEP004164

Qian Yang, CAS,2023.08.29

Description

OEP004485

Qian Yang, CAS,2023.08.29

Description

OEP004488

Qian Yang, CAS,2023.08.29

Description

OEP004489

Chunchun Yuan, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China,2023.01.16

Description

OEP003842

Wenran Li, Chinese academy of sciences,2023.11.27

Description

This study analyzed two Chinese cohorts derived from a large Chinese population study, the Shanghai Changfeng Study, composing of individuals consecutively enrolled from Shanghai Changfeng Community, Shanghai from June 2009 to December 2012. Samples included Han Chinese individuals who were randomly sampled from the Shanghai Changfeng study and generated genome-wide DNA methylation profiles in the whole blood tissue. Changes in DNA methylation reflect effects of environmental changes on the human genome and may help us to explain the link between obesity and environmental factors.

OEP004768