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Lung and Thoracic cancer
MLL4 Regulates the Progression of Non–Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis
Yang Yang, Rongfang Qiu, Qiaoyou Weng, Ziwei Xu, Jingjing Song, Siyu Zhao, Miaomiao Meng, Dengke Zhang, Chunli Kong, Hailin Wang, Min Xu, Zhongwei Zhao, Jiansong Ji
Cancer Res Treat. 2023;55(3):778-803.   Published online January 26, 2023
DOI: https://doi.org/10.4143/crt.2022.1042
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis.
Materials and Methods
RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis.
Results
We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties.
Conclusion
Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.

Citations

Citations to this article as recorded by  
  • Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer
    Linxiang Zhang, Xueying Zhang, Yan Shi, Yuhan Ni, Jiaojiao Fei, Zhixin Jin, Wenjuan Li, Xiaojing Wang, Nan Wu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • The multifaceted role of SOX2 in breast and lung cancer dynamics
    Kiavash Hushmandi, Seyed Hassan Saadat, Seyedalireza Mirilavasani, Salman Daneshi, Amir Reza Aref, Noushin Nabavi, Rasoul Raesi, Afshin Taheriazam, Mehrdad Hashemi
    Pathology - Research and Practice.2024; 260: 155386.     CrossRef
  • PIK3IP1: structure, aberration, function, and regulation in diseases
    Yingjie Jia, Pengxing He, Xubin Ma, Kaili Lv, Ying Liu, Yichao Xu
    European Journal of Pharmacology.2024; 977: 176753.     CrossRef
  • UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
    Li He, Heng Chen, Bin Ruan, Li He, Ming Luo, Yulun Fu, Rui Zou
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Role of histone methyltransferase KMT2D in BMSC osteogenesis via AKT signaling
    Zhichun Zhang, Yanyan Guo, Xuejun Gao, Xiaoyan Wang, Chanyuan Jin
    Regenerative Therapy.2024; 26: 775.     CrossRef
  • Landscape of targeted therapies for lung squamous cell carcinoma
    Qiuxuan Chen, Xiaoshuo Zheng, Weiting Cheng, Jian Li
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • 4,701 View
  • 283 Download
  • 6 Web of Science
  • 6 Crossref
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Head and Neck cancer
Long-term Survivals, Toxicities and the Role of Chemotherapy in Early-Stage Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy: A Retrospective Study with 15-Year Follow-up
Lin Wang, Jingjing Miao, Huageng Huang, Boyu Chen, Xiao Xiao, Manyi Zhu, Yingshan Liang, Weiwei Xiao, Shaomin Huang, Yinglin Peng, Xiaowu Deng, Xing Lv, Weixiong Xia, Yanqun Xiang, Xiang Guo, Fei Han, Chong Zhao
Cancer Res Treat. 2022;54(1):118-129.   Published online June 7, 2021
DOI: https://doi.org/10.4143/crt.2021.101
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients.
Materials and Methods
Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010.
Results
With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group.
Conclusion
Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.

Citations

Citations to this article as recorded by  
  • Retrospective analysis of 1539 nasopharyngeal carcinoma cases: chemotherapy should not be excluded for non-Asian patients with T1-2N1M0 stage
    Xin-Yu Li, Chang-Ying Zhong, Hui-Xian Xu
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Genistein and chlorin E6-loaded versatile nanoformulation for remodeling the hypoxia-related tumor microenvironment and boosting photodynamic therapy in nasopharyngeal carcinoma treatment
    Qiang Zhou, Quazi T. H. Shubhra, Peng Lai, Jiayi Shi, Chenhao Fang, Qian Guo, Wanqing Li, Rui Chen, Xinkun Shen, Lina Huang, Xiaojun Cai, Sen Lin
    Advanced Composites and Hybrid Materials.2025;[Epub]     CrossRef
  • Radiation oncology for the rhinologist
    Helena Levyn, Fan Yang, Nancy Y. Lee
    Current Opinion in Otolaryngology & Head & Neck Surgery.2024; 32(1): 5.     CrossRef
  • Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey
    Victor C. W. Tam, Jerry C. F. Ching, Sindy S. T. Yip, Virginia H. Y. Kwong, Catherine P. L. Chan, Kenneth C. W. Wong, Shara W. Y. Lee
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Multifactorial clinical analysis of factors affecting necrosis of nasal septal mucosal flap after salvage surgery for recurrent nasopharyngeal carcinoma
    Qilin Gong, Huaying Li, Hui Liu, Youyuan Shi
    Scientific Reports.2024;[Epub]     CrossRef
  • Long noncoding RNA LINC00173 induces radioresistance in nasopharyngeal carcinoma via inhibiting CHK2/P53 pathway
    Jingjing Miao, Boyu Chen, Yunyun Xiao, Runda Huang, Xiao Xiao, Shunzhen Lu, Lu Zhang, Xuguang Wang, Ying Ouyang, Xiangfu Chen, Qiuyan Chen, Yanqun Xiang, Xiang Guo, Xiaowu Deng, Lin Wang, Haiqiang Mai, Chong Zhao
    Cancer Gene Therapy.2023; 30(9): 1249.     CrossRef
  • Therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development through HSPA5/NFκB/CD55 pathway in nasopharyngeal carcinoma
    Chengcong Chen, Anbang Ren, Qi Yi, Jiazuo Cai, Muhammad Khan, Yunen Lin, Zhong Huang, Jie Lin, Jian Zhang, Wei Liu, Anan Xu, Yunhong Tian, YaWei Yuan, Ronghui Zheng
    Clinical and Experimental Immunology.2023; 213(2): 221.     CrossRef
  • Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review)
    Huageng Huang, Yuyi Yao, Xinyi Deng, Zongyao Huang, Yungchang Chen, Zhao Wang, Huangming Hong, He Huang, Tongyu Lin
    International Journal of Oncology.2023;[Epub]     CrossRef
  • Quality of life and swallowing outcomes after early proactive swallowing rehabilitation by either transcutaneous neuromuscular electrical stimulation or exercise‐based swallowing training in patients with nasopharyngeal carcinoma after radiotherapy
    Peter K. M. Ku, Alexander C. Vlantis, Rita W. M. Wong, Thomas S. C. Hui, Thomas Law, Louisa K. Y. Ng, Eddy W. Y. Wong, W. T. Chang, David R. Johnson, Florence S. T. Mok, K. H. Wong, Victor Abdullah, Andrew van Hasselt, Kathy Y. S. Lee, Michael C. F. Tong
    Laryngoscope Investigative Otolaryngology.2023; 8(6): 1532.     CrossRef
  • Prognostic nutritional index and serum lactate dehydrogenase predict the prognosis of nasopharyngeal carcinoma patients who received intensity-modulated radiation therapy
    Chunxia Zhang, Zhouwei Zhan, Yunxiang Fang, Yuanyuan Ruan, Mingan Lin, Zhisen Dai, Yanping Zhang, Shanshan Yang, Shuxiang Xiao, Bijuan Chen
    Journal of Cancer Research and Clinical Oncology.2023; 149(20): 17795.     CrossRef
  • A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma
    Yao-Can Xu, Kai-Hua Chen, Zhong-Guo Liang, Xiao-Dong Zhu
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Minimally Invasive Surgery for Early-Stage Nasopharyngeal Carcinoma
    Jinping Liu, Zesheng Zeng, Dingting Wang, Gang Qin
    Journal of Craniofacial Surgery.2022; 33(8): e834.     CrossRef
  • External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma
    Pui-Lam Yip, Shing-Fung Lee, Cheuk-Wai Horace Choi, Po-Chung Sunny Chan, Ka-Wai Alice Cheung, Chung-Hang James Chow, Ka-Man Cheung, Wing-Yu Jessica Lai, Ho-Fun Victor Lee, Ka-On Lam, Chi-Leung Chiang, Chun-Yin Edwin Wong, Ming-Chun Darren Poon, Macy Tong,
    Cancers.2021; 13(17): 4286.     CrossRef
  • 7,205 View
  • 174 Download
  • 14 Web of Science
  • 13 Crossref
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Gastrointestinal cancer
Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis
Yuan Zhang, Lufei Zhang, Sinan Lu, Yucheng Xiang, Cheng Zeng, Tianyu He, Yuan Ding, Weilin Wang
Cancer Res Treat. 2021;53(1):184-198.   Published online October 5, 2020
DOI: https://doi.org/10.4143/crt.2020.192
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear.
Materials and Methods
Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry.
Results
CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway.
Conclusion
CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Citations

Citations to this article as recorded by  
  • Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA
    Qingshan Cai, Dongyang Wu, Yueling Shen, Shudong Li, Liyou Liu, Dong Liu, Yong Li, Xiaonan Chen, Limin Wang, Jianxing Zheng
    Medicine.2024; 103(5): e35859.     CrossRef
  • The effect of genetics and biochemistry on the pathogenesis of cholangiocarcinoma
    Mete Ucdal, Ayse Burus, Basak Celtikci
    International Journal of Hepatobiliary and Pancreatic Diseases.2024; 14(2): 1.     CrossRef
  • Interplay between lncRNAs and the PI3K/AKT signaling pathway in the progression of digestive system neoplasms (Review)
    Xiaoyu Zhang, Lei Shi, Mengzhen Xing, Chunjing Li, Fengjun Ma, Yuning Ma, Yuxia Ma
    International Journal of Molecular Medicine.2024;[Epub]     CrossRef
  • A review on the role of ncRNAs in the pathogenesis of cholangiocarcinoma
    Soudeh Ghafouri-Fard, Arash Safarzadeh, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Samsami
    International Journal of Biological Macromolecules.2023; 225: 809.     CrossRef
  • A Novel CASC15-ALK and TFG-ROS1 Fusion Observed in Uterine Inflammatory Myofibroblastic Tumor
    Bin Chang, Zhe Wang, Min Ren, Qianlan Yao, Lu Zhao, Xiaoyan Zhou
    International Journal of Gynecological Pathology.2023; 42(5): 451.     CrossRef
  • Development and validation of combined Ki67 status prediction model for intrahepatic cholangiocarcinoma based on clinicoradiological features and MRI radiomics
    Xianling Qian, Changwu Zhou, Fang Wang, Xin Lu, Yunfei Zhang, Lei Chen, Mengsu Zeng
    La radiologia medica.2023; 128(3): 274.     CrossRef
  • Non-Coding RNA in Cholangiocarcinoma: An Update
    Jiehan Li, Haolin Bao, Ziyue Huang, Zixin Liang, Ning Lin, Chunjie Ni, Yi Xu
    Frontiers in Bioscience-Landmark.2023;[Epub]     CrossRef
  • A study of the prognostic value of long non-coding RNA CASC15 in human solid tumors utilizing The Cancer Genome Atlas (TCGA) datasets and a meta-analysis
    Weiwei Chen, Wenqi Qian, Jun Nie, Mintao Dai
    Clinical and Experimental Medicine.2022;[Epub]     CrossRef
  • Long Non-Coding RNAs as Molecular Biomarkers in Cholangiocarcinoma
    Yanhua Wu, Khizar Hayat, Yufei Hu, Jianfeng Yang
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
  • Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway
    Ziyan Chen, Bangjie He, Jungang Zhao, Jiacheng Li, Yifeng Zhu, Leilei Li, Wenming Bao, Jiuyi Zheng, Haitao Yu, Gang Chen
    Phytomedicine.2022; 104: 154323.     CrossRef
  • Cystic angiomatosis in children: clinical experience and review of literature
    Wen Chao Li, Li Liu, Zhen Dong Wang, Hui Chen, Guang Liu, Zhi Chun Feng
    World Journal of Surgical Oncology.2022;[Epub]     CrossRef
  • A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma
    Pei-Jian Zhang, Meng-Dong Liu, Fang-Yong Fan, Ke-Xia Liu
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151–5p/WNT7A axis
    Dongfang Bai, Chong Guo, Aimin Wang, Guolong Pang, Jing Gao, Chuan Wang, Dapeng Zhao, Jie Yang, Jianmin Ren
    Pathology - Research and Practice.2021; 225: 153561.     CrossRef
  • LncRNA CASC15 Promotes Cerebral Ischemia/Reperfusion Injury via miR-338-3p/ETS1 Axis in Acute Ischemic Stroke
    Chen Chen, Linjing Wang, Li Wang, Qi Liu, Chunying Wang
    International Journal of General Medicine.2021; Volume 14: 6305.     CrossRef
  • Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma
    Li Guo, Yuyang Dou, Yifei Yang, Shiqi Zhang, Yihao Kang, Lulu Shen, Lihua Tang, Yaodong Zhang, Changxian Li, Jun Wang, Tingming Liang, Xiangcheng Li
    Computational and Structural Biotechnology Journal.2021; 19: 5722.     CrossRef
  • 7,513 View
  • 178 Download
  • 15 Web of Science
  • 15 Crossref
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