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Nishiyama H, Niinuma T, Kitajima H, Ishiguro K, Yamamoto E, Sudo G, Sasaki H, Yorozu A, Aoki H, Toyota M, Kai M, Suzuki H. HOXA11-As Promotes Lymph Node Metastasis Through Regulation of IFNL and HMGB Family Genes in Pancreatic Cancer. Int J Mol Sci 2024; 25:12920. [PMID: 39684631 DOI: 10.3390/ijms252312920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 11/26/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
Recent studies have shown that long noncoding RNAs (lncRNAs) play pivotal roles in the development and progression of cancer. In the present study, we aimed to identify lncRNAs associated with lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). We analyzed data from The Cancer Genome Atlas (TCGA) database to screen for genes overexpressed in primary PDAC tumors with lymph node metastasis. Our screen revealed 740 genes potentially associated with lymph node metastasis, among which were multiple lncRNA genes located in the HOXA locus, including HOXA11-AS. Elevated expression of HOXA11-AS was associated with more advanced tumor stages and shorter overall survival in PDAC patients. HOXA11-AS knockdown suppressed proliferation and migration of PDAC cells. RNA-sequencing analysis revealed that HOXA11-AS knockdown upregulated interferon lambda (IFNL) family genes and downregulated high-mobility group box (HMGB) family genes in PDAC cells. Moreover, HMGB3 knockdown suppressed proliferation and migration by PDAC cells. These results suggest that HOXA11-AS contributes to PDAC progression, at least in part, through regulation of IFNL and HMGB family genes and that HOXA11 AS is a potential therapeutic target in PDAC.
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Affiliation(s)
- Hayato Nishiyama
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Takeshi Niinuma
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Hiroshi Kitajima
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Kazuya Ishiguro
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Eiichiro Yamamoto
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Gota Sudo
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Hajime Sasaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Akira Yorozu
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Hironori Aoki
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Mutsumi Toyota
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Masahiro Kai
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
| | - Hiromu Suzuki
- Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
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2
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Zhang YW, Wu SX, Wang GW, Wan RD, Yang QE. Single-cell analysis identifies critical regulators of spermatogonial development and differentiation in cattle-yak bulls. J Dairy Sci 2024; 107:7317-7336. [PMID: 38642661 DOI: 10.3168/jds.2023-24442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/11/2024] [Indexed: 04/22/2024]
Abstract
Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable to or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.
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Affiliation(s)
- Yi-Wen Zhang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810000, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shi-Xin Wu
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810000, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Guo-Wen Wang
- Qinghai Academy of Animal Husbandry and Veterinary Sciences, Xining, Qinghai 810016, China
| | - Rui-Dong Wan
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810000, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qi-En Yang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810000, China; University of Chinese Academy of Sciences, Beijing 100049, China; Qinghai Key Laboratory of Animal Ecological Genomics, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China.
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3
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Yao M, Fang RF, Xie Q, Xu M, Sai WL, Yao DF. Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:2350-2361. [PMID: 38994143 PMCID: PMC11236219 DOI: 10.4251/wjgo.v16.i6.2350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/02/2024] [Accepted: 04/24/2024] [Indexed: 06/13/2024] Open
Abstract
The prevention and early diagnosis of liver cancer remains a global medical challenge. During the malignant transformation of hepatocytes, a variety of oncogenic cellular signalling molecules, such as novel high mobility group-Box 3, angiopoietin-2, Golgi protein 73, glypican-3, Wnt3a (a signalling molecule in the Wnt/β-catenin pathway), and secretory clusterin, can be expressed and secreted into the blood. These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy. This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.
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Affiliation(s)
- Min Yao
- Department of Immunology, Medical School of Nantong University and Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Rong-Fei Fang
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Qun Xie
- Department of Infectious Diseases, Haian People’s Hospital, Haian 226600, Jiangsu Province, China
| | - Min Xu
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Department of Immunology, Medical School of Nantong University and Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Yao M, Fang RF, Xie Q, Xu M, Sai WL, Yao DF. Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:2814-2825. [DOI: 10.4251/wjgo.v16.i6.2814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/02/2024] [Accepted: 04/24/2024] [Indexed: 06/13/2024] Open
Abstract
The prevention and early diagnosis of liver cancer remains a global medical challenge. During the malignant transformation of hepatocytes, a variety of oncogenic cellular signalling molecules, such as novel high mobility group-Box 3, angiopoietin-2, Golgi protein 73, glypican-3, Wnt3a (a signalling molecule in the Wnt/β-catenin pathway), and secretory clusterin, can be expressed and secreted into the blood. These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy. This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.
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Affiliation(s)
- Min Yao
- Department of Immunology, Medical School of Nantong University and Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Rong-Fei Fang
- Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Qun Xie
- Department of Infectious Diseases, Haian People’s Hospital, Haian 226600, Jiangsu Province, China
| | - Min Xu
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Wen-Li Sai
- Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Deng-Fu Yao
- Department of Immunology, Medical School of Nantong University and Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Iori S, D'Onofrio C, Laham-Karam N, Mushimiyimana I, Lucatello L, Lopparelli RM, Gelain ME, Capolongo F, Pauletto M, Dacasto M, Giantin M. Establishment and characterization of cytochrome P450 1A1 CRISPR/Cas9 Knockout Bovine Foetal Hepatocyte Cell Line (BFH12). Cell Biol Toxicol 2024; 40:18. [PMID: 38528259 PMCID: PMC10963470 DOI: 10.1007/s10565-024-09856-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Accepted: 03/21/2024] [Indexed: 03/27/2024]
Abstract
The cytochrome P450 1A (CYP1A) subfamily of xenobiotic metabolizing enzymes (XMEs) consists of two different isoforms, namely CYP1A1 and CYP1A2, which are highly conserved among species. These two isoenzymes are involved in the biotransformation of many endogenous compounds as well as in the bioactivation of several xenobiotics into carcinogenic derivatives, thereby increasing the risk of tumour development. Cattle (Bos taurus) are one of the most important food-producing animal species, being a significant source of nutrition worldwide. Despite daily exposure to xenobiotics, data on the contribution of CYP1A to bovine hepatic metabolism are still scarce. The CRISPR/Cas9-mediated knockout (KO) is a useful method for generating in vivo and in vitro models for studying xenobiotic biotransformations. In this study, we applied the ribonucleoprotein (RNP)-complex approach to successfully obtain the KO of CYP1A1 in a bovine foetal hepatocyte cell line (BFH12). After clonal expansion and selection, CYP1A1 excision was confirmed at the DNA, mRNA and protein level. Therefore, RNA-seq analysis revealed significant transcriptomic changes associated with cell cycle regulation, proliferation, and detoxification processes as well as on iron, lipid and mitochondrial homeostasis. Altogether, this study successfully generates a new bovine CYP1A1 KO in vitro model, representing a valuable resource for xenobiotic metabolism studies in this important farm animal species.
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Affiliation(s)
- Silvia Iori
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Caterina D'Onofrio
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Nihay Laham-Karam
- University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences, Neulaniementie 2, 70211, Kuopio, Finland
| | - Isidore Mushimiyimana
- University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences, Neulaniementie 2, 70211, Kuopio, Finland
| | - Lorena Lucatello
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Rosa Maria Lopparelli
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Maria Elena Gelain
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Francesca Capolongo
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Marianna Pauletto
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Mauro Dacasto
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy
| | - Mery Giantin
- Department of Comparative Biomedicine and Food Science, University of Padua, Viale Dell'Università 16, Legnaro, 35020, Padua, Italy.
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Ji F, Yao Z, Liu C, Fu S, Ren B, Liu Y, Ma L, Wei J, Sun D. A novel lnc-LAMC2-1:1 SNP promotes colon adenocarcinoma progression by targeting miR-216a-3p/HMGB3. Heliyon 2022; 8:e12342. [PMID: 36582685 PMCID: PMC9792752 DOI: 10.1016/j.heliyon.2022.e12342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 09/01/2022] [Accepted: 12/06/2022] [Indexed: 12/23/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) was associated with altering the secondary structure of long non-coding RNA (lncRNA). Increasing reports showed that lnc-LAMC2-1:1 SNP played an important role in cancer development and invasion. This study is to elucidate the molecular function of lnc-LAMC2-1:1 SNP rs2147578 promoting tumor progression in colon adenocarcinoma (COAD). In this study, we found that the lnc-LAMC2-1:1 SNP rs2147578 was upregulated in COAD cell lines. Furthermore, lnc-LAMC2-1:1 SNP rs2147578 promoted colon cancer migration, invasion, and proliferation. Interestingly, lnc-LAMC2-1:1 SNP rs2147578 positively regulated HMGB3 expression via miR-216a-3p in colon cancer cells. Functional enrichment analysis showed that targeting genes of miR-216a-3p were enriched in regulating the pluripotency of stem cells, MAPK signaling pathway, TNF signaling pathway, neurotrophin signaling pathway, relaxin signaling pathway, and FoxO signaling pathway. Tumor Immune Estimation Resource (TIMER) database revealed that there was a significantly positive correlation between HMGB3 expression and the infiltration of CD8+ T cells, B cells, neutrophils, macrophages, and CD4+ T cells. Finally, HMGB3 overexpression was validated in external data. In conclusions, lnc-LAMC2-1:1 SNP rs2147578 was involved in promoting COAD progression by targeting miR-216a-3p/HMGB3, and this study will provide a novel molecular target for COAD.
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Affiliation(s)
- Fulong Ji
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Zhiwei Yao
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Chunxiang Liu
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Siqi Fu
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Bingbing Ren
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Yong Liu
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Lushun Ma
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Jianming Wei
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China,Corresponding author.
| | - Daqing Sun
- Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China,Corresponding author.
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Sharma P, Yadav P, Sundaram S, Venkatraman G, Bera AK, Karunagaran D. HMGB3 inhibition by miR-142-3p/sh-RNA modulates autophagy and induces apoptosis via ROS accumulation and mitochondrial dysfunction and reduces the tumorigenic potential of human breast cancer cells. Life Sci 2022; 304:120727. [PMID: 35753437 DOI: 10.1016/j.lfs.2022.120727] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 02/07/2023]
Abstract
AIMS High mobility group box (HMGB) family proteins, HMGB1, HMGB2, HMGB3, and HMGB4 are oncogenic. The oncogenic nature of HMGB1 is characterized by its association with autophagy, ROS, and MMP. Since HMGB3 is its paralog, we hypothesized that it might also modulate autophagy, ROS, and MMP. Hence, we targeted HMGB3 using its shRNA or miR-142-3p and assessed the changes in autophagy, ROS, MMP, and tumorigenic properties of human breast cancer cells. MAIN METHODS Cell viability was assessed by resazurin staining and annexin-V/PI dual staining was used for confirming apoptosis. Colony formation, transwell migration, invasion and luciferase reporter (for miRNA-target validation) assays were also performed. ROS and MMP were detected using DHE and MitoTracker dyes, respectively. A zebrafish xenograft model was used to assess the role of miR-142-3p on in vivo metastatic potential of breast cancer cells. KEY FINDINGS Breast cancer tissues from Indian patients and TCGA samples exhibit overexpression of HMGB3. miR-142-3p binds to 3' UTR of HMGB3, leading to its downregulation that subsequently inhibits colony formation and induces apoptosis involving increased ROS accumulation and decreased MMP, phospho-mTOR and STAT3. Our findings show that HMGB3 is directly involved in the miR-142-3p-mediated disruption of autophagy and induction of apoptotic cell death via modulation of LC3, cleaved PARP and Bcl-xL. In addition, miR-142-3p inhibited migration, invasion and metastatic potential of breast cancer cells. SIGNIFICANCE Our findings highlighted the role of HMGB3, for the first time, in the modulation of autophagy and apoptosis in human breast cancer cells, and these results have therapeutic implications.
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Affiliation(s)
- Priyanshu Sharma
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
| | - Poonam Yadav
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
| | - Sandhya Sundaram
- Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai 600116, India
| | - Ganesh Venkatraman
- Department of Human Genetics, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Chennai 600116, India
| | - Amal Kanti Bera
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
| | - Devarajan Karunagaran
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India.
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Wen B, Wei YT, Zhao K. The role of high mobility group protein B3 (HMGB3) in tumor proliferation and drug resistance. Mol Cell Biochem 2021; 476:1729-1739. [PMID: 33428061 DOI: 10.1007/s11010-020-04015-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023]
Abstract
The high mobility group protein B (HMGB) family (including HMGB1, HMGB2, HMGB3, and HMGB4) can regulate the mechanisms of DNA replication, transcription, recombination, and repair, and act as cytokines to mediate responses to infection, injury, and inflammation. HMGB1/2/3 has a high similarity in sequence and structure, while HMGB4 has no acidic C-terminal tail. Among them, HMGB3 can regulate the self-renewal and differentiation of normal hematopoietic stem cell population, but the decrease of its expression is easy to induce leukemia. Up-regulation of its expression promotes tumor development and chemotherapy resistance through a variety of mechanisms, and non-coding RNA can regulate to promote tumor cell proliferation, invasion, and migration and inhibit cancer cell apoptosis.
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Affiliation(s)
- Bin Wen
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, P. R. China
| | - Ying-Ting Wei
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, P. R. China
| | - Kui Zhao
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, P. R. China.
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Poluan RH, Sudigyo D, Rahmawati G, Setiasari DW, Sesotyosari SL, Wardana T, Astuti I, Heriyanto DS, Indrasari SR, Herawati C, Afiahayati , Haryana SM. Transcriptome Related to Avoiding Immune Destruction in Nasopharyngeal Cancer in Indonesian Patients Using Next-Generation Sequencing. Asian Pac J Cancer Prev 2020; 21:2593-2601. [PMID: 32986357 PMCID: PMC7779461 DOI: 10.31557/apjcp.2020.21.9.2593] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Indexed: 12/24/2022] Open
Abstract
Objective: This study aims to obtain the transcriptomes profile associated with avoiding immune destruction from nasopharyngeal cancer patients in Indonesia using next-generation sequencing. Methods: The samples are divided into two types of samples; 1) biopsy of nasopharyngeal cancer tissue samples, 2) brushing tissue of people without nasopharyngeal cancer as control samples. The sequencing results were mapped (HISAT2) and quantified (HTSeq) for differential expression analysis using edgeR software. Transcripts data analyzed with Pantherdb and DAVID software to find genes related to the immune system and pathways related to immune destruction by cancer. Results: The differential expression results show that 2,046 genes that have a significant differential expression. The 90 genes expression has down-regulated and 1,956 genes expression up-regulated, there are 20 genes related to the immune system. The 20 genes related to the immune system by analyzing lionproject.net that directly related to hallmark avoiding immune destruction that genes are CXCL9/10/11. The gene expression of CXCL9/10/11 regulates PD-L1 expressions via the Jak/STAT signaling pathway. The interaction between the extracellular domain PD-1 and PD-L1 in cancer cells have avoiding immune destruction. Conclusion: The results of this study suggest that the gene expression of CXCL9/10/11 have up-regulated is related to avoiding immune destruction that can use as an early detection biomarker of nasopharyngeal cancer in Indonesian patients.
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Affiliation(s)
- Risky Hiskia Poluan
- Study Program of Biotechnology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Digdo Sudigyo
- Study Program of Biotechnology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Gisti Rahmawati
- Study Program of Biotechnology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | | | | | - Tirta Wardana
- Universitas Jenderal Soedirman, Central Java, Indonesia
| | - Indwiani Astuti
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Didik Setyo Heriyanto
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Sagung Rai Indrasari
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | | | - - Afiahayati
- Department of Computer Science and Electronics, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Sofia Mubarika Haryana
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Gu J, Xu T, Huang QH, Zhang CM, Chen HY. HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1α. Cancer Manag Res 2019; 11:5075-5089. [PMID: 31213919 PMCID: PMC6549700 DOI: 10.2147/cmar.s204357] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 04/10/2019] [Indexed: 01/18/2023] Open
Abstract
Background: Breast cancer is the most common malignant tumor that affects women with higher incidence. High-mobility group box 3 (HMGB3) plays critical functions in DNA repair, recombination, transcription and replication. This study aimed to investigate the effects of HMGB3 silence on mammosphere formation and tumor growth of breast cancer. Methods: LV5-HMGB3 and LV3-siHMGB3 vectors were transfected into MCF10A, MDA-MB-231, HCC1937, ZR-75-1 and MCF7 cells. Cell counting kit-8 (CCK-8) assay was used to evaluate cell proliferation. Xenograft tumor mice model was established by injection of MDA-MB-231. qRT-PCR and western blot were used to examine the expression of Nanog, Sox2 and OCT-4. Mammosphere forming assay was employed to evaluate mammosphere formation both in vivo and in vitro. Dual luciferase assay was utilized to verify the interaction between HMGB3 and hypoxia-inducible factor 1α (HIF1α). CD44+/CD24− was assessed with flow cytometry. Results: HMGB3 expression was higher significantly (p<0.05) in cancer cells compared to normal cells. HMGB3 overexpression significantly (p<0.05) enhanced and HMGB3 silence reduced cell proliferative mice compared to MCF10A and MDA-MB-231, respectively. HMGB3 overexpression enhanced and HMGB3 silence inhibited mammosphere formation. HMGB3 overexpression upregulated and HMGB3 silence downregulated Nanog, SOX2 and OCT-4 genes/proteins in MCF10A and MDA-MB-231 cells, respectively. HMGB3 silence reduced CD44+/CD24− levels in cancer cells. Silence of HMGB3 strengthened reductive effects of PTX on tumor sizes, iPSC biomarkers and mammosphere amounts in xenograft tumor mouse models. HMGB3 silence inhibited mammoshpere formation, cell proliferation and CD44+CD24− by interacting with HIF1α. Conclusion: HMGB3 silence could inhibit the cell proliferation in vitro and suppress tumor growth in vivo levels. The antitumor effects of HMGB3 silence were mediated by interacting with the HIF1α.
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Affiliation(s)
- Jun Gu
- Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China
| | - Tao Xu
- Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China
| | - Qin-Hua Huang
- Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China
| | - Chu-Miao Zhang
- Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China
| | - Hai-Yan Chen
- Department of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, People's Republic of China
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Zheng W, Yang J, Dong Z, Wang L, Fang M, Wu W, Yao D, Yao M. High mobility group box 3 as an emerging biomarker in diagnosis and prognosis of hepatocellular carcinoma. Cancer Manag Res 2018; 10:5979-5989. [PMID: 30538547 PMCID: PMC6255278 DOI: 10.2147/cmar.s181742] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE High mobility group box 3 (HMGB3) is associated with hepatocytes malignant transformation by our previous work. We continued to investigate the diagnostic and prognostic values of HMGB3 for hepatocellular carcinoma (HCC). PATIENTS AND METHODS Circulating HMGB3 levels were quantitatively detected in a cohort of 225 patients with chronic liver diseases by ELISA and compared with alpha-fetoprotein by the receiver operating characteristic curve. HMGB3 expression in tissues of 170 HCC was detected by tissue microarray and immunohistochemistry. Relationship between HMGB3 level and HCC prognosis was evaluated by the Kaplan-Meier curves and Cox regression model. RESULTS The incidence of serum HMGB3 >2.0 ng/mL was 75.6% in HCC (96/127), 20.8% in liver cirrhosis (10/48), 16.0% in chronic hepatitis (8/50), and none in healthy controls (0/49). Significant difference (P<0.001) of circulating HMGB3 level was found between HCC and benign liver diseases. Total diagnostic sensitivity of serum HMGB3 plus alpha-fetoprotein was up to 89.0% for HCC. Higher HMGB3 expression was confirmed to be 73.5% in HCC tissues (125/170) >30.6% in their paracancerous tissues (52/170). HMGB3 expression was closely related to tumor size, TNM stage, poor survival, and high recurrence, suggesting an independent prognosis factor for HCC. CONCLUSION HMGB3 with aberrant expression could be a novel diagnostic and prognostic marker for HCC.
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Affiliation(s)
- Wenjie Zheng
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
| | - Li Wang
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
| | - Miao Fang
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
| | - Wei Wu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Dengfu Yao
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China,
| | - Min Yao
- Medical School of Nantong University, Nantong 226001, Jiangsu, China, ,
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