|
1
|
Li K, Zhao D, Liu X, Cao Q, Ruan L, Lei H, Chen X, Jin X, Li Q, Xie X, Di C. Long Non-Coding TP73-AS1: A Potential Biomarker and Therapeutic Target in Cancer. Int J Mol Sci 2025; 26:3886. [PMID: 40332793 PMCID: PMC12028249 DOI: 10.3390/ijms26083886] [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: 02/26/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 05/08/2025] Open
Abstract
Tumor protein 73 antisense RNA 1 (TP73-AS1), a newly discovered long non-coding RNA (lncRNA), the dysregulated expression of which is closely related to the occurrence, drug resistance, and prognosis of various cancers. Exploring the regulatory mechanism of TP73-AS1 provides a new research direction for cancer diagnosis and treatment. On this basis, we briefly review the molecular structural and dual regulatory roles of TP73-AS1 in cancer. In addition, we outline its three molecular mechanisms in cancer: binding to proteins, regulating signaling pathways, and serving as molecular sponges. Subsequently, we introduce the role of TP73-AS1 in common malignant tumors such as gastric cancer (GC), lung cancer, colorectal cancer (CRC), etc. Last, emphasis is given to the potential clinical value of TP73-AS1, especially as single nucleotide polymorphisms of this lncRNA are associated with the risk of GC and CRC. Therefore, this review highlights the significance of TP73-AS1 as a novel biomarker and therapeutic target.
Collapse
Affiliation(s)
- Kejing Li
- School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
| | - Dapeng Zhao
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xuena Liu
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Qiyou Cao
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China
| | - Longzhu Ruan
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Huiwen Lei
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xiaohua Chen
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xiaodong Jin
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Qiang Li
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
- Advanced Energy Science and Technology Guangdong Laboratory, Huizhou 516029, China
| | - Xiaodong Xie
- School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Cuixia Di
- Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
- Advanced Energy Science and Technology Guangdong Laboratory, Huizhou 516029, China
| |
Collapse
|
|
2
|
Jiang YK, Li W, Qiu YY, Yue M. Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer. World J Gastrointest Oncol 2024; 16:2318-2334. [PMID: 38994153 PMCID: PMC11236256 DOI: 10.4251/wjgo.v16.i6.2318] [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: 12/11/2023] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 06/13/2024] Open
Abstract
Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance. Human epidermal growth factor receptor 2 (HER2) is one of the most important targets in targeted therapy for gastric cancer. Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer. The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified. However, monoclonal antibodies, due to their large molecular weight, inability to penetrate the blood-brain barrier, and drug resistance, lead to decreased therapeutic efficacy, so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer. Small-molecule tyrosine kinase inhibitors, such as lapatinib and pyrrotinib, have the advantages of small molecular weight, penetrating the blood-brain barrier and high oral bioavailability, and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future. Antibo-drug conjugate, such as T-DM1 and T-DXd, can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing, and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab. Therefore, after more detailed stratification of gastric cancer patients, various gastric cancer drugs targeting HER2 are expected to play a more significant role.
Collapse
Affiliation(s)
- Ya-Kun Jiang
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Wei Li
- Health Management Center, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| | - Ying-Yang Qiu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Meng Yue
- Department of Gastroenterology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
| |
Collapse
|
|
3
|
Gao SS, Zhang ZK, Wang XB, Ma Y, Yin GQ, Guo XB. Role of transcribed ultraconserved regions in gastric cancer and therapeutic perspectives. World J Gastroenterol 2022; 28:2900-2909. [PMID: 35978878 PMCID: PMC9280734 DOI: 10.3748/wjg.v28.i25.2900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/08/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is the fourth leading cause of cancer-related death. The occurrence and development of GC is a complex process involving multiple biological mechanisms. Although traditional regulation modulates molecular functions related to the occurrence and development of GC, the comprehensive mechanisms remain unclear. Ultraconserved region (UCR) refers to a genome sequence that is completely conserved in the homologous regions of the human, rat and mouse genomes, with 100% identity, without any insertions or deletions, and often located in fragile sites and tumour-related genes. The transcribed UCR (T-UCR) is transcribed from the UCR and is a new type of long noncoding RNA. Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC, revealing a new mechanism underlying GC. Therefore, this article aims to review the relevant research on T-UCRs in GC, as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC, to provide new strategies for GC diagnosis and treatment.
Collapse
Affiliation(s)
- Shen-Shuo Gao
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Zhi-Kai Zhang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
| | - Xu-Bin Wang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Yan Ma
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Guo-Qing Yin
- Department of Anus and Intestine Surgery, Qingzhou Hospital Affiliated to Shandong First Medical University, Qingzhou 262500, Shandong Province, China
| | - Xiao-Bo Guo
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong Province, China
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| |
Collapse
|
|
4
|
Chen C, Wang J, Feng Y, Liang Y, Huang Y, Zou W. TP73-AS1 as a predictor of clinicopathological parameters and prognosis in human malignancies: a meta and bioinformatics analysis. BMC Cancer 2022; 22:581. [PMID: 35614413 PMCID: PMC9134685 DOI: 10.1186/s12885-022-09658-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 05/11/2022] [Indexed: 11/28/2022] Open
Abstract
Background Long non-coding RNA P73 antisense RNA 1 T (non-protein coding), also known as Lnc RNA TP73-AS1, is dysregulated in various tumors but the correlation between its expression and clinicopathological parameters and/or prognoses in cancer patients is inconclusive. Here, we performed a meta-analysis to evaluate the prognostic value of Lnc RNA TP73-AS1 for malignancies. Methods We systematically searched four online databases including PubMed, the Web of Science, Embase, and the Cochrane Library for eligible articles published up to June 29/2020. Odds ratios (ORs) and Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the association of TP73-AS1 expression with prognostic and clinicopathological parameters. We further validated TP73-AS1 expression in various malignancies and its potential prognostic value using the GEPIA online database. We predicted potential biological processes and relevant signal mechanisms through the public databases. Results A total of 26 studies examining 14 cancers were analyzed to evaluate the relationship between TP73-AS1 expression, clinicopathological features and prognostic indicators. The results indicated that TP73-AS1 expression markedly correlates with TNM stage (OR = 3.27,95% CI:2.43–4.39, P < 0.00001), tumor size (OR = 3.00, 95%CI:2.08–4.35, P < 0.00001), lymph node metastasis (OR = 2.77, 95%CI:1.42–5.38,P < 0.00001) and distant metastasis (OR = 4.50,95%CI:2. 62–7.73,P < 0.00001). No correlation with age (OR = 1.12,95%CI:0.77–1.64, P > 0.05), gender (OR = 1.08, 95%CI:0.84–1.38, P > 0.05) or differentiation (OR = 1.39, 95%CI:0.71–2.70, P = 0.340) was observed. TP73-AS1 overexpression was a biomarker of poor Overall survival(OS)(HR = 1.85,95%CI:1.53–2.22, P < 0.00001) and Disease-Free-Survival (DFS) (HR = 1.57,95%CI:1.03–2.42, P < 0.05). Dysregulated TP73-AS1 expression and its prognostic value in various cancers was validated based on The Cancer Genome Atlas (TCGA). Further biological function predictions indicated that TP73-AS1 was involved in pro-oncogenic signaling. Conclusions The upregulation of Lnc RNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies.
Collapse
Affiliation(s)
- Caizhi Chen
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Jingjing Wang
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Yeqian Feng
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Ye Liang
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Yan Huang
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China
| | - Wen Zou
- Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.
| |
Collapse
|
|
5
|
MiR-223 Promotes Tumor Progression via Targeting RhoB in Gastric Cancer. JOURNAL OF ONCOLOGY 2022; 2022:6708871. [PMID: 35035482 PMCID: PMC8758265 DOI: 10.1155/2022/6708871] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/10/2021] [Accepted: 12/13/2021] [Indexed: 12/14/2022]
Abstract
Gastric cancer (GC) is among the most prevalent causes of cancer-related death globally. MiR-223 has been implicated in a variety of cellular mechanisms linked to cancer progression. However, the miR-223 expressions and its function in GC are unknown. We discovered that miR-223 expression was raised in GC tissues in comparison with nearby normal tissues in this investigation. Additionally, multiplied miR-223 expression was strongly linked with TNM stage (p=0.022), live metastasis (p=0.004),lymph node metastasis (p=0.004),and Borrmann type and was associated with an unfavorable prognostic for patients with GC. Furthermore, suppressing miR-223 significantly increased cell death and prevented cell migration and invasion in vitro. Additionally, miR-223 silencing decreased tumor development in vivo. Additionally, we discovered that miR-223 enhanced GC development by specifically targeting RhoB. In summary, our findings reveal that miR-223 increases tumor progression in GC by targeting RhoB, suggesting that it could serve to be a potential biomarker for the prediction of the disease.
Collapse
|
|
6
|
Yuan Z, Zhang Y, Chen P, Liu S, Xin L, Liu C. Long non-coding RNA HLA complex group 18 promotes gastric cancer progression by targeting microRNA-370-3p expression. J Pharm Pharmacol 2021; 74:250-258. [PMID: 34618022 DOI: 10.1093/jpp/rgab134] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 08/18/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Our research was aimed at investigating the biological character of human leukocyte antigen complex group 18 (HCG18) on gastric cancer (GC) progression and its potential mechanisms. METHODS The expression characteristics and prognostic values of HCG18 in GC were evaluated through the GEPIA database and Kaplan-Meier plotter database. Quantitative real-time PCR and Western blot were used for quantification of messenger RNA expression, microRNA (miRNA) expression and protein expression. Cell proliferation, migration and invasion were detected by cell counting kit-8 assay, 5'-bromo-2'-deoxyuridine assay and Transwell assay, respectively. Dual-luciferase reporter gene assay and RNA immunoprecipitation assay were used for examination of the interactions among HCG18, miR-370-3p and epidermal growth factor receptor (EGFR) 3'UTR. KEY FINDINGS HCG18 expression was up-regulated in GC tissues, and its high expression was closely associated with increased tumour size, advanced TNM stage, poor differentiation of tumour tissues and unfavourable prognosis of patients with GC. Additionally, HCG18 overexpression promoted the proliferation, migration and invasion of GC cells, and its knockdown suppressed the malignant phenotypes of GC cells. Furthermore, HCG18 served as a miRNA sponge to repress miR-370-3p and indirectly up-regulated EGFR expression in GC cells. CONCLUSIONS HCG18 served as a tumour-promoting factor in GC progression by modulating the miR-370-3p/EGFR axis.
Collapse
Affiliation(s)
- Zhi Yuan
- Department of Internal Medicine, Xinglin Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Yuan Zhang
- Department of Internal Medicine, Xinglin Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Peng Chen
- Department of Emergency, Xinglin Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Shuhong Liu
- Department of Radiotherapy, Linyi Cancer Hospital, Linyi, Shandong, China
| | - Li Xin
- Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong, China
| | - Chengxia Liu
- Department of Pathology, Linyi Cancer Hospital, Linyi, Shandong, China
| |
Collapse
|
|
7
|
Guang B, Liu X, Liang T. Effect of miRNA-223-3p Targeting Stromal Interaction Molecule 1 on Proliferation and Apoptosis of Hypoxia/Reoxygenation-Applied H9c2 Cardiomyocytes. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
This study was established to determine the effect of miRNA-223-3p on the proliferation and apoptosis of hypoxia/reoxygenation-applied H9c2 cardiomyocytes and the associated mechanisms. A hypoxia/reoxygenation (H/R) model was established, with normal cells also used as a control. miRNA-NC,
miRNA-223-3p, anti-miRNA-NC, and anti-miRNA-223-3p plasmids were transfected into normally cultured cardiomyocytes, defined as the miRNA-NC, miRNA-223-3p, anti-miRNA-NC, and anti-miRNA-223-3p groups. In addition, miRNA-223-3p was co-transfected into normally cultured cardiomyocytes with pcDNA3.1
and pcDNA3.1-STIM1 plasmids, followed by treatment with H/R for cells in the miR-NC and miR-223-3p groups, defined as the H/R+miRNA-NC, H/R+miRNA-223-3p, H/R+miRNA-223-3p+pcDNA3.1, and H/R+miRNA-223-3p+pcDNA3.1-STIM1 groups. A liposome method was adopted for assessing transfection. qRT-PCR
was used to detect miRNA-223-3p expression, while western blotting was used to detect protein expression. MTT assay was used to detect cell viability, flow cytometry to detect apoptosis, and dual luciferase reporter gene assay to detect fluorescence activity. After H/R treatment, miR-223-3p,
cyclin D1, and Bcl-2 expression of cardiomyocytes decreased, p21 and Bax expression significantly increased, cell activity decreased, and the apoptosis rate increased. miRNA-223-3p achieved the targeted regulation of STIM1 expression. miRNA-223-3p overexpression promoted the H/R-induced cardiomyocyte
proliferation and inhibited cardiomyocyte apoptosis. STIM1 overexpression reversed the proliferation-promoting and apoptosis-inhibiting effects of miRNA-223-3p on cardiomyocytes treated with H/R. The findings show that miRNA-223-3p overexpression promotes H/R-induced cell proliferation, inhibits
apoptosis, and protects H/R-induced cardiomyocytes from injury, via a mechanism probably associated with STIM1 expression. miRNA-223-3p thus provides a new target for treating cardiomyocyte injury.
Collapse
Affiliation(s)
- Bin Guang
- Department of Cardiology, Jinzhong First People’s Hospital, Jinzhong 030600, Shanxi, PR China
| | - Xiaoqin Liu
- Department of Cardiology, Jinzhong First People’s Hospital, Jinzhong 030600, Shanxi, PR China
| | - Tingchen Liang
- Department of Cardiology, Jinzhong First People’s Hospital, Jinzhong 030600, Shanxi, PR China
| |
Collapse
|
|
8
|
Zhu J, Han S. Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/β-catenin pathway. IUBMB Life 2021; 73:690-704. [PMID: 33481334 DOI: 10.1002/iub.2450] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 12/16/2020] [Accepted: 12/24/2020] [Indexed: 12/15/2022]
Abstract
Dysfunction of histone deacetylase 10 (HDAC10) has been suggested in the carcinogenesis of cervical cancer (CC). However, its association with microRNAs (miRNAs) in CC remains exclusive. Hence, this study aims to probe the role of HDAC10 in regulating CC cell proliferation, migration, and invasion and its correlation with the screened-out miRNA target. Microarray analysis and RT-qPCR revealed that HDAC10 expressed poorly in CC cells relative to human immortalized endocervical cells (End1/E6E7). Moreover, HDAC10 downregulation predicted poor survival for patients with CC. Overexpression of HDAC10 reduced CC cell biological activities in vitro and tumor growth and lung metastases in vivo. miR-223, upregulated in CC, was regulated by HDAC10 through histone acetylation, while miR-223 inhibited the effects of HDAC10 overexpression in CC. miR-223 targeted the 3'-UTR of thioredoxin interacting protein (TXNIP) and suppressed its expression, leading to increased CC development in vitro and in vivo. TXNIP overexpression impaired Wnt/β-catenin pathway activity in CC cells.
Collapse
Affiliation(s)
- Jinming Zhu
- Department of Oncology, Affiliated Zhongshan Hospital, Dalian University, Dalian, P.R. China
| | - Shichao Han
- Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, P.R. China
| |
Collapse
|