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4. QDPR deficiency drives immune suppression in pancreatic cancer

Author

Liu, Ji, He, Xiaowei, Deng, Shuang, Zhao, Sihan, Zhang, Shaoping, Chen, Ziming, Xue, Chunling, Zeng, Lingxing, Zhao, Hongzhe, Zhou, Yifan, Bai, Ruihong, Xu, Zilan, Liu, Shaoqiu, Zhou, Quanbo, Li, Mei, Zhang, Jialiang, Huang, Xudong, Chen, Rufu, Wang, Liqin, Lin, Dongxin, and Zheng, Jian

Published
2024
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10. Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial

Author

Qin, Tingting, Zhang, Hang, Pan, Shutao, Liu, Jun, Li, Dewei, Chen, Rufu, Huang, Xiaobing, Liu, Yahui, Liu, Jianhua, Cheng, Wei, Chen, Xuemin, Zhao, Wenxing, Li, Jingdong, Tan, Zhijian, Huang, Heguang, Li, Deyu, Zhu, Feng, Yu, Guangsheng, Zhou, Baoyong, Zheng, Shangyou, Tang, Yichen, Ke, Jianji, Liu, Xueqing, Chen, Botao, Chen, Weibo, Ma, Hongqin, Xu, Jian, Liu, Yifeng, Lin, Ronggui, Dong, Yadong, Yu, Yahong, Wang, Min, and Qin, Renyi

Published
2024
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11. Effect of Laparoscopic and Open Pancreatoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial

Author

Qin, Tingting, Zhang, Hang, Pan, Shutao, Liu, Jun, Li, Dewei, Chen, Rufu, Huang, Xiaobing, Liu, Yahui, Liu, Jianhua, Cheng, Wei, Chen, Xuemin, Zhao, Wenxing, Li, Jingdong, Tan, Zhijian, Huang, Heguang, Li, Deyu, Zhu, Feng, Yu, Guangsheng, Zhou, Baoyong, Zheng, Shangyou, Tang, Yichen, Ke, Jianji, Liu, Xueqing, Chen, Botao, Chen, Weibo, Ma, Hongqin, Xu, Jian, Liu, Yifeng, Lin, Ronggui, Dong, Yadong, Yu, Yahong, Wang, Min, and Qin, Renyi

Published
2023
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12. The short- and long-term outcomes of laparoscopic pancreaticoduodenectomy combining with different type of mesentericoportal vein resection and reconstruction for pancreatic head adenocarcinoma: a Chinese multicenter retrospective cohort study

Author

Ouyang, Guoqing, Zhong, Xiaosheng, Cai, Zhiwei, Liu, Jianhua, Zheng, Shangyou, Hong, Defei, Yin, Xinmin, Yu, Jian, Bai, Xueli, Liu, Yahui, Liu, Jun, Huang, Xiaobing, Xiong, Yong, Xu, Jie, Cai, Yunqiang, Jiang, Zhongyi, Chen, Rufu, and Peng, Bing

Published
2023
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19. Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial

Author

Wang, Min, Li, Dewei, Chen, Rufu, Huang, Xiaobing, Li, Jing, Liu, Yahui, Liu, Jianhua, Cheng, Wei, Chen, Xuemin, Zhao, Wenxing, Li, Jingdong, Tan, Zhijian, Huang, Heguang, Li, Deyu, Zhu, Feng, Qin, Tingting, Ma, Jingdong, Yu, Guangsheng, Zhou, Baoyong, Zheng, Shangyou, Tang, Yichen, Han, Wei, Meng, Lingyu, Ke, Jianji, Feng, Feng, Chen, Botao, Yin, Xinmin, Chen, Weibo, Ma, Hongqin, Xu, Jian, Liu, Yifeng, Lin, Ronggui, Dong, Yadong, Yu, Yahong, Liu, Jun, Zhang, Hang, and Qin, Renyi

Published
2021
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20. Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models.

Author

Zheng, Shangyou, Hu, Chonghui, Lin, Qing, Li, Tingting, Li, Guolin, Tian, Qing, Zhang, Xiang, Huang, Tianhao, Ye, Yuancheng, He, Rihua, Chen, Changhao, Zhou, Yu, and Chen, Rufu

Subjects
PANCREATIC cancer, SCIATIC nerve injuries, PANCREATIC tumors, LABORATORY mice, DORSAL root ganglia, FIBROBLASTS, ANIMAL disease models
Abstract

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)–dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer. Editor's summary: Pancreatic cancer has a very poor prognosis and is often characterized by perineural invasion (PNI); however, the role that PNI plays in postoperative survival has been unexplored. Here, Zheng et al. evaluate the role PNI plays in pancreatic cancer prognosis and show that cancer-associated fibroblasts (CAFs) induce PNI in tumors through CAF-derived extracellular vesicles (EVs). They show that these EVs are packaged with PNI-associated transcript (PIAT) that enhances PNI in mouse models and induces worse survival. PIAT represents a potential target for reducing PNI in pancreatic cancer and perhaps improving survival for patients that requires further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Published
2024
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22. Characterization of gut microbiota in patients with stage 3–4 chronic kidney disease: a retrospective cohort study

Author

Yang, Xiali, primary, Cai, Shiying, additional, Gong, Jinsheng, additional, Zhang, Jun, additional, Lian, Minling, additional, Chen, Rufu, additional, Zhou, Linghui, additional, Bai, Peijin, additional, Liu, Bo, additional, Zhuang, Minting, additional, Tan, Honghong, additional, Xu, Juan, additional, and Li, Meizhen, additional

Published
2023
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25. LINC00842 inactivates transcription co-regulator PGC-1α to promote pancreatic cancer malignancy through metabolic remodelling

Author

Huang, Xudong, Pan, Ling, Zuo, Zhixiang, Li, Mei, Zeng, Lingxing, Li, Rui, Ye, Ying, Zhang, Jialiang, Wu, Guandi, Bai, Ruihong, Zhuang, Lisha, Wei, Lusheng, Zheng, Yanfen, Su, Jiachun, Deng, Junge, Deng, Shuang, Zhang, Shaoping, Zhu, Shihao, Che, Xu, Wang, Chengfeng, Wu, Chen, Chen, Rufu, Lin, Dongxin, and Zheng, Jian

Published
2021
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26. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer

Author

Chen, Changhao, Luo, Yuming, He, Wang, Zhao, Yue, Kong, Yao, Liu, Hongwei, Zhong, Guangzheng, Li, Yuting, Li, Jun, Huang, Jian, Chen, Rufu, and Lin, Tianxin

Subjects
Vascular endothelial growth factor -- Health aspects, Cancer metastasis -- Prognosis -- Health aspects, Antisense RNA -- Health aspects, Endothelium, Endothelial growth factors, RNA, Tumors, Cancer patients, Health care industry
Abstract

Patients with bladder cancer (BCa) with clinical lymph node (LN) metastasis have an extremely poor prognosis. VEGF-C has been demonstrated to play vital roles in LN metastasis in BCa. However, approximately 20% of BCa with LN metastasis exhibits low VEGF-C expression, suggesting a VEGF-C-independent mechanism for LN metastasis of BCa. Herein, we demonstrate that BCa cell-secreted exosome-mediated lymphangiogenesis promoted LN metastasis in BCa in a VEGF-C-independent manner. We identified an exosomal long noncoding RNA (lncRNA), termed lymph node metastasis-associated transcript 2 (LNMAT2), that stimulated human lymphatic endothelial cell (HLEC) tube formation and migration in vitro and enhanced tumor lymphangiogenesis and LN metastasis in vivo. Mechanistically, LNMAT2 was loaded to BCa cell-secreted exosomes by directly interacting with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1). Subsequently, exosomal LNMAT2 was internalized by HLECs and epigenetically upregulated prospero homeobox 1 (PROX1) expression by recruitment of hnRNPA2B1 and increasing the H3K4 trimethylation level in the PROX1 promoter, ultimately resulting in lymphangiogenesis and lymphatic metastasis. Therefore, our findings highlight a VEGF-C-independent mechanism of exosomal lncRNA-mediated LN metastasis and identify LNMAT2 as a therapeutic target for LN metastasis in BCa., Introduction Bladder cancer (BCa), one of the most commonly diagnosed malignancies worldwide, is the leading cause of cancer-related death among men, with an estimated 550,000 new cases and 20,000 deaths [...]

Published
2020
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27. KRAS mutant-driven SUMOylation controls extracellular vesicle transmission to trigger lymphangiogenesis in pancreatic cancer

Author

Luo, Yuming, Li, Zhihua, Kong, Yao, He, Wang, Zheng, Hanhao, An, Mingjie, Lin, Yan, Zhang, Dingwen, Yang, Jiabin, Zhao, Yue, Chen, Changhao, and Chen, Rufu

Subjects
Gene mutations -- Health aspects -- Physiological aspects, Metastasis -- Risk factors, Pancreatic cancer -- Genetic aspects -- Complications and side effects, Company growth, Health care industry
Abstract

Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC) and predicts poor prognosis for patients. The [KRAS.sup.G12D] mutation confers an aggressive PDAC phenotype that is susceptible to lymphatic dissemination. However, the regulatory mechanism underlying [KRAS.sup.G12D] mutation-driven LN metastasis in PDAC remains unclear. Herein, we found that PDAC with the [KRAS.sup.G12D] mutation ([KRAS.sup.G12D] PDAC) sustained extracellular vesicle-mediated (EV-mediated) transmission of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in a SUMOylation-dependent manner and promoted lymphangiogenesis and LN metastasis in vitro and in vivo. Mechanistically, hnRNPA1 bound with SUMO2 at the lysine 113 residue via [KRAS.sup.G12D]-induced hyperactivation of SUMOylation, which enabled its interaction with TSG101 to enhance hnRNPA1 packaging and transmission via EVs. Subsequently, SUMOylation induced EV-packaged-hnRNPA1 anchoring to the adenylateand uridylate-rich elements of PROX1 in lymphatic endothelial cells, thus stabilizing PROX1 mRNA. Importantly, impeding SUMOylation of EV-packaged hnRNPA1 dramatically inhibited LN metastasis of [KRAS.sup.G12D] PDAC in a genetically engineered [Kras.sup.G12D/+] [Trp53.sup.R172H/+] Pdx-1-Cre (KPC) mouse model. Our findings highlight the mechanism by which KRAS mutant-driven SUMOylation triggers EV-packaged hnRNPA1 transmission to promote lymphangiogenesis and LN metastasis, shedding light on the potential application of hnRNPA1 as a therapeutic target in patients with [KRAS.sup.G12D] PDAC., Introduction Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive system cancers and represents the seventh leading cause of cancer-related death worldwide (1, 2). Accumulating reports have shown [...]

Published
2022
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28. Data from N6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer

Author

Su, Jiachun, primary, Li, Rui, primary, Chen, Ziming, primary, Liu, Shaoqiu, primary, Zhao, Hongzhe, primary, Deng, Shuang, primary, Zeng, Lingxing, primary, Xu, Zilan, primary, Zhao, Sihan, primary, Zhou, Yifan, primary, Li, Mei, primary, He, Xiaowei, primary, Liu, Ji, primary, Xue, Chunling, primary, Bai, Ruihong, primary, Zhuang, Lisha, primary, Zhou, Quanbo, primary, Zhang, Shaoping, primary, Chen, Rufu, primary, Huang, Xudong, primary, Lin, Dongxin, primary, Zheng, Jian, primary, and Zhang, Jialiang, primary

Published
2023
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30. Supplementary Data from N6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer

Author

Su, Jiachun, primary, Li, Rui, primary, Chen, Ziming, primary, Liu, Shaoqiu, primary, Zhao, Hongzhe, primary, Deng, Shuang, primary, Zeng, Lingxing, primary, Xu, Zilan, primary, Zhao, Sihan, primary, Zhou, Yifan, primary, Li, Mei, primary, He, Xiaowei, primary, Liu, Ji, primary, Xue, Chunling, primary, Bai, Ruihong, primary, Zhuang, Lisha, primary, Zhou, Quanbo, primary, Zhang, Shaoping, primary, Chen, Rufu, primary, Huang, Xudong, primary, Lin, Dongxin, primary, Zheng, Jian, primary, and Zhang, Jialiang, primary

Published
2023
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31. Supplementary Data from Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma

Author

Kong, Yao, primary, Luo, Yuming, primary, Zheng, Shangyou, primary, Yang, Jiabin, primary, Zhang, Dingwen, primary, Zhao, Yue, primary, Zheng, Hanhao, primary, An, Mingjie, primary, Lin, Yan, primary, Ai, Le, primary, Diao, Xiayao, primary, Lin, Qing, primary, Chen, Changhao, primary, and Chen, Rufu, primary

Published
2023
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32. Consensus of clinical diagnosis and treatment for non-functional pancreatic neuroendocrine neoplasms with diameter <2 cm

Author

Wu, Wenming, primary, Cai, Shouwang, additional, Chen, Rufu, additional, Fu, Deliang, additional, Ge, Chunlin, additional, Hao, Chunyi, additional, Hao, Jihui, additional, Huang, Heguang, additional, Jian, Zhixiang, additional, Jin, Gang, additional, Li, Fei, additional, Li, Haimin, additional, Li, Shengping, additional, Li, Weiqin, additional, Li, Yixiong, additional, Liang, Tingbo, additional, Liu, Xubao, additional, Lou, Wenhui, additional, Miao, Yi, additional, Mou, Yiping, additional, Peng, Chenghong, additional, Qin, Renyi, additional, Shao, Chenghao, additional, Sun, Bei, additional, Tan, Guang, additional, Wang, Huaizhi, additional, Wang, Lei, additional, Wang, Wei, additional, Wang, Weilin, additional, Wei, Junmin, additional, Wu, Heshui, additional, Wu, Zheng, additional, Yan, Changqing, additional, Yang, Yinmo, additional, Yin, Xiaoyu, additional, Yu, Xianjun, additional, Yuan, Chunhui, additional, and Zhao, Yupei, additional

Published
2023
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37. Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression

Author

Pan, Ling, Huang, Xudong, Liu, Ze-Xian, Ye, Ying, Li, Rui, Zhang, Jialiang, Wu, Guandi, Bai, Ruihong, Zhuang, Lisha, Wei, Lusheng, Li, Mei, Zheng, Yanfen, Su, Jiachun, Deng, Junge, Deng, Shuang, Zeng, Lingxing, Zhang, Shaoping, Wu, Chen, Che, Xu, Wang, Chengfeng, Chen, Rufu, Lin, Dongxin, and Zheng, Jian

Subjects
Cytokines -- Health aspects, Transfer RNA -- Health aspects, Pancreatic cancer -- Development and progression -- Genetic aspects -- Care and treatment, Health care industry
Abstract

The tumorigenic mechanism for pancreatic ductal adenocarcinoma (PDAC) is not clear, although chronic inflammation is implicated. Here, we identified an inflammatory cytokine-regulated transfer RNA- derived (tRNA-derived) fragment, tRF-21VBY9PYKHD (tRF-21), as a tumor suppressor in PDAC progression. We found that the biogenesis of tRF-21 could be inhibited by leukemia inhibitory factor and IL-6 via the splicing factor SRSF5. Reduced tRF- 21 promoted AKT2/1-mediated heterogeneous nuclear ribonucleoprotein L (hnRNP L) phosphorylation, enhancing hnRNP L to interact with dead-box helicase 17 (DDX17) to form an alternative splicing complex. The provoked hnRNP L-DDX17 activity preferentially spliced Caspase 9 and mH2A1 pre-mRNAs to form Caspase9b and mH2A1.2, promoting PDAC cell malignant phenotypes. The tRF-21 levels were significantly lower in PDACs than in normal tissues, and patients with low tRF-21 levels had a poor prognosis. Treatment of mouse PDAC xenografts or patient-derived xenografts (PDXs) with tRF-21 mimics repressed tumor growth and metastasis. These results demonstrate that tRF-21 has a tumor-suppressive effect and is a potential therapeutic agent for PDAC., Introduction Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy, with a 5-year survival rate of less than 9% (1, 2). Most PDAC tumors are already in an advanced stage [...]

Published
2021
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38. Practice Patterns and Perioperative Outcomes of Laparoscopic Pancreaticoduodenectomy in China: A Retrospective Multicenter Analysis of 1029 Patients

Author

Wang, Min, Peng, Bing, Liu, Jianhua, Yin, Xinmin, Tan, Zhijian, Liu, Rong, Hong, Defei, Zhao, Wenxing, Wu, Heshui, Chen, Rufu, Li, Dewei, Huang, Heguang, Miao, Yi, Liu, Yahui, Liang, Tingbo, Wang, Wei, Cai, Yunqiang, Xing, Zhongqiang, Cheng, Wei, Zhong, Xiaosheng, Zhao, Zhiming, Zhang, Jungang, Yang, Zhiyong, Li, Guolin, Shao, Yue, Lin, Guirong, Jiang, Kuirong, Wu, Pengfei, Jia, Baoxing, Ma, Tao, Jiang, Chongyi, Peng, Shuyou, and Qin, Renyi

Published
2021
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40. Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma

Author

Kong, Yao, primary, Luo, Yuming, additional, Zheng, Shangyou, additional, Yang, Jiabin, additional, Zhang, Dingwen, additional, Zhao, Yue, additional, Zheng, Hanhao, additional, An, Mingjie, additional, Lin, Yan, additional, Ai, Le, additional, Diao, Xiayao, additional, Lin, Qing, additional, Chen, Changhao, additional, and Chen, Rufu, additional

Published
2023
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41. N 6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer

Author

Su, Jiachun, primary, Li, Rui, additional, Chen, Ziming, additional, Liu, Shaoqiu, additional, Zhao, Hongzhe, additional, Deng, Shuang, additional, Zeng, Lingxing, additional, Xu, Zilan, additional, Zhao, Sihan, additional, Zhou, Yifan, additional, Li, Mei, additional, He, Xiaowei, additional, Liu, Ji, additional, Xue, Chunling, additional, Bai, Ruihong, additional, Zhuang, Lisha, additional, Zhou, Quanbo, additional, Zhang, Shaoping, additional, Chen, Rufu, additional, Huang, Xudong, additional, Lin, Dongxin, additional, Zheng, Jian, additional, and Zhang, Jialiang, additional

Published
2023
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44. Supplementary Tables from N6-methyladenosine–Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression

Author

Deng, Junge, primary, Zhang, Jialiang, primary, Ye, Ying, primary, Liu, Kaijing, primary, Zeng, Lingxing, primary, Huang, Jingyi, primary, Pan, Ling, primary, Li, Mei, primary, Bai, Ruihong, primary, Zhuang, Lisha, primary, Huang, Xudong, primary, Wu, Guandi, primary, Wei, Lusheng, primary, Zheng, Yanfen, primary, Su, Jiachun, primary, Zhang, Shaoping, primary, Chen, Rufu, primary, Lin, Dongxin, primary, and Zheng, Jian, primary

Published
2023
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45. Supplementary Data 2 from N6-methyladenosine–Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression

Author

Deng, Junge, primary, Zhang, Jialiang, primary, Ye, Ying, primary, Liu, Kaijing, primary, Zeng, Lingxing, primary, Huang, Jingyi, primary, Pan, Ling, primary, Li, Mei, primary, Bai, Ruihong, primary, Zhuang, Lisha, primary, Huang, Xudong, primary, Wu, Guandi, primary, Wei, Lusheng, primary, Zheng, Yanfen, primary, Su, Jiachun, primary, Zhang, Shaoping, primary, Chen, Rufu, primary, Lin, Dongxin, primary, and Zheng, Jian, primary

Published
2023
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46. Supplementary Figures from N6-methyladenosine–Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression

Author

Deng, Junge, primary, Zhang, Jialiang, primary, Ye, Ying, primary, Liu, Kaijing, primary, Zeng, Lingxing, primary, Huang, Jingyi, primary, Pan, Ling, primary, Li, Mei, primary, Bai, Ruihong, primary, Zhuang, Lisha, primary, Huang, Xudong, primary, Wu, Guandi, primary, Wei, Lusheng, primary, Zheng, Yanfen, primary, Su, Jiachun, primary, Zhang, Shaoping, primary, Chen, Rufu, primary, Lin, Dongxin, primary, and Zheng, Jian, primary

Published
2023
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