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| 1 | An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk,local immunosuppression and tumor progression显示文摘Dissecting and understanding the cancer ecosystem,especially that around the tumor margins,which have strong implications for tumor cell infiltration and invasion,are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments.Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing(Stereo-seq),we identified a 500µm-wide zone centered around the tumor border in patients with liver cancer,referred to as“the invasive zone”.We detected strong immunosuppression,metabolic reprogramming,and severely damaged hepatocytes in this zone.We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2(referred to collectively as SAAs)located close to the border on the paratumor side.Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes,which subsequently caused SAAs’overexpression in these hepatocytes.Furthermore,overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization,further promoting local immunosuppression,potentially resulting in tumor progression.Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer(n=423)showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis.Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth.The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis,but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors. | Liang Wu Jiayan Yan Yinqi Bai Feiyu Chen Xuanxuan Zou Jiangshan Xu Ao Huang Liangzhen Hou Yu Zhong Zehua Jing Qichao Yu Xiaorui Zhou Zhifeng Jiang Chunqing Wang Mengnan Cheng Yuan Ji Yingyong Hou Rongkui Luo Qinqin Li Liang Wu Jianwen Cheng Pengxiang Wang Dezhen Guo Waidong Huang Junjie Lei Shang Liu Yizhen Yan Yiling Chen Sha Liao Yuxiang Li Haixiang Sun Na Yao Xiangyu Zhang Shiyu Zhang Xi Chen Yang Yu Yao Li Fengming Liu Zheng Wang Shaolai Zhou Huanming Yang Shuang Yang Xun Xu Longqi Liu Qiang Gao Zhaoyou Tang Xiangdong Wang Jian Wang Jia Fan Shiping Liu Xinrong Yang Ao Chen Jian Zhou | 2023 | Cell Research2023，33，8： | 1 |
| 2 | Preparation and characterization of polyacrylamide-intercalated graphite oxide显示文摘 | Jiayan Xu Yuan Hu Lei Song Qingan Wang Weicheng Fan | 2001 | Materials Research Bulletin2001，，10： | 1 |
| 3 | A novel MYCN-YTHDF1 cascade contributes to retinoblastoma tumor growth by eliciting m^(6)A-dependent activation of multiple oncogenes显示文摘Retinoblastoma, the most prevalent primary intraocular tumor in children, leads to vision impairment, disability and even death.In addition to RB1 inactivation, MYCN activation has been documented as another common oncogenic alteration in retinoblastoma and represents one of the high-risk molecular subtypes of retinoblastoma. However, how MYCN contributes to the progression of retinoblastoma is still incompletely understood. Here, we report that MYCN upregulates YTHDF1, which encodes one of the reader proteins for N6-methyladenosine(m^(6)A) RNA modification, in retinoblastoma. We further found that this MYCN-upregulated m^(6)A reader functions to promote retinoblastoma cell proliferation and tumor growth in an m^(6)A bindingdependent manner. Mechanistically, YTHDF1 promotes the expression of multiple oncogenes by binding to their m RNAs and enhancing m RNA stability and translation in retinoblastoma cells. Taken together, our findings reveal a novel MYCN-YTHDF1regulatory cascade in controlling retinoblastoma cell proliferation and tumor growth, pinpointing an unprecedented mechanism for MYCN amplification and/or activation to promote retinoblastoma progression. | Yingxiu Luo Mengjia He Jie Yang Feifei Zhang Jie Chen Xuyang Wen Jiayan Fan Xianqun Fan Peiwei Chai Renbing Jia | 2023 | Science China(Life Sciences)2023，66，9： | 0 |
| 4 | Novel insights into histone lysine methyltransferases in cancer therapy:From epigenetic regulation to selective drugs显示文摘The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers. | Qili Liao Jie Yang Shengfang Ge Peiwei Chai Jiayan Fan Renbing Jia | 2023 | Journal of Pharmaceutical Analysis2023，13，2： | 0 |
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