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Saimaiti W, Ma J, Dilimulati P, Wang Y. Sunitinib-resistant renal cell carcinoma cell-derived exosomes promote facilitation of tumor progression via secretion of the lncRNA SNHG16. Hum Cell 2025; 38:100. [PMID: 40358820 DOI: 10.1007/s13577-025-01228-5] [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: 02/05/2025] [Accepted: 05/01/2025] [Indexed: 05/15/2025]
Abstract
Renal cell carcinoma (RCC) is one of the most common tumors of high malignancy in the urological system. Sunitinib is commonly used to treat RCC, while drug resistance severely limited the therapeutic efficacy. Tumor-derived exosomes play important roles in facilitating cancer development. However, the role of drug-resistant tumor-derived exosomes in tumorigenesis and resistance of RCC has not been elucidated. Here we isolated sunitinib-sensitive/resistant RCC cells-derived exosomes, characterized by transmission electron microscopy (TEM) and western blot. Furthermore, co-culture experiments were performed and we found that sunitinib-resistant RCC cells-derived exosomes (R-exos) promoted cell proliferation and upregulated proliferation-related genes cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA) expression, and inhibited apoptosis and the expression of Bax and Caspase-3 of sunitinib-resistant RCC (RCC/R) cells by delivering lncRNA small nuclear RNA host gene 16 (SNHG16). In resistant cell-derived xenograft (CDX-R) models, R-exos induced tumor growth in vivo, while knockdown of SNHG16 effectively diminished the tumorigenesis of RCC. Moreover, SNHG16 positively regulated the expression of trophinin associated protein (TROAP) by sponging miR-106a-5p in RCC cells, whereas inhibition of miR-106a-5p or overexpression of TROAP greatly reversed the suppression of tumorigenesis and sunitinib resistant by silencing SNHG16. R-exos lncRNA SNHG16 promoted sunitinib resistant and malignant progress by regulating the miR-106a-5p/TROAP axis, and targeting SNHG16/miR-106a-5p/TROAP axis may be a novel therapeutic approach for sunitinib-treated patients of RCC.
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Affiliation(s)
- WeiLijiang Saimaiti
- Department of Pediatric Urology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830054, China
| | - Jun Ma
- Department of Urology, First Affiliated Hospital, Xinjiang Medical University, No. 137, Liyuushan South Road, Urumqi, 830054, Xinjiang, China
| | - Paluoke Dilimulati
- Department of Pediatric Urology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830054, China
| | - Yujie Wang
- Department of Urology, First Affiliated Hospital, Xinjiang Medical University, No. 137, Liyuushan South Road, Urumqi, 830054, Xinjiang, China.
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2
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Li J, Li Y, Fu L, Chen H, Du F, Wang Z, Zhang Y, Huang Y, Miao J, Xiao Y. Targeting ncRNAs to overcome metabolic reprogramming‑mediated drug resistance in cancer (Review). Int J Oncol 2025; 66:35. [PMID: 40116120 PMCID: PMC12002672 DOI: 10.3892/ijo.2025.5741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/07/2025] [Indexed: 03/23/2025] Open
Abstract
The emergence of resistance to antitumor drugs in cancer cells presents a notable obstacle in cancer therapy. Metabolic reprogramming is characterized by enhanced glycolysis, disrupted lipid metabolism, glutamine dependence and mitochondrial dysfunction. In addition to promoting tumor growth and metastasis, metabolic reprogramming mediates drug resistance through diverse molecular mechanisms, offering novel opportunities for therapeutic intervention. Non‑coding RNAs (ncRNAs), a diverse class of RNA molecules that lack protein‑coding function, represent a notable fraction of the human genome. Due to their distinct expression profiles and multifaceted roles in various cancers, ncRNAs have relevance in cancer pathophysiology. ncRNAs orchestrate metabolic abnormalities associated with drug resistance in cancer cells. The present review provides a comprehensive analysis of the mechanisms by which metabolic reprogramming drives drug resistance, with an emphasis on the regulatory roles of ncRNAs in glycolysis, lipid metabolism, mitochondrial dysfunction and glutamine metabolism. Furthermore, the present review aimed to discuss the potential of ncRNAs as biomarkers for predicting chemotherapy responses, as well as emerging strategies to target ncRNAs that modulate metabolism, particularly in the context of combination therapy with anti‑cancer drugs.
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Affiliation(s)
- Junxin Li
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Yanyu Li
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Lin Fu
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Huiling Chen
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Fei Du
- Department of Pharmacy, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, Sichuan 64200, P.R. China
| | - Zhongshu Wang
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Yan Zhang
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Yu Huang
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Jidong Miao
- Department of Oncology, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
| | - Yi Xiao
- Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, P.R. China
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Zhang W, Xia M, Li J, Liu G, Sun Y, Chen X, Zhong J. Warburg effect and lactylation in cancer: mechanisms for chemoresistance. Mol Med 2025; 31:146. [PMID: 40264038 PMCID: PMC12016192 DOI: 10.1186/s10020-025-01205-6] [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: 02/18/2025] [Accepted: 04/09/2025] [Indexed: 04/24/2025] Open
Abstract
In the clinical management of cancers, the emergence of chemoresistance represents a profound and imperative "pain point" that requires immediate attention. Understanding the mechanisms of chemoresistance is essential for developing effective therapeutic strategies. Importantly, existing studies have demonstrated that glucose metabolic reprogramming, commonly referred to as the Warburg effect or aerobic glycolysis, is a major contributor to chemoresistance. Additionally, lactate, a byproduct of aerobic glycolysis, functions as a signaling molecule that supports lysine lactylation modification of proteins, which also plays a critical role in chemoresistance. However, it is insufficient to discuss the role of glycolysis or lactylation in chemoresistance from a single perspective. The intricate relationship between aerobic glycolysis and lactylation plays a crucial role in promoting chemoresistance. Thus, a thorough elucidation of the mechanisms underlying chemoresistance mediated by aerobic glycolysis and lactylation is essential. This review provides a comprehensive overview of these mechanisms and further outlines that glycolysis and lactylation exert synergistic effects, promoting the development of chemoresistance and creating a positive feedback loop that continues to mediate this resistance. The close link between aerobic glycolysis and lactylation suggests that the application of glycolysis-related drugs or inhibitors in cancer therapy may represent a promising anticancer strategy. Furthermore, the targeted application of lactylation, either alone or in combination with other treatments, may offer new therapeutic avenues for overcoming chemoresistance.
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Affiliation(s)
- Wenjie Zhang
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Min Xia
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Jiahui Li
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Gaohua Liu
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Yan Sun
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Xisha Chen
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Jing Zhong
- Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
- Institute of Cancer Research, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
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Mao S, Li J, Huang J, Lv L, Zhang Q, Cheng Q, Liu X, Bi Z, Yao J. Therapeutic potential of microRNA-506 in cancer treatment: mechanisms and therapeutic implications. Front Oncol 2025; 15:1524763. [PMID: 40248198 PMCID: PMC12003368 DOI: 10.3389/fonc.2025.1524763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 03/17/2025] [Indexed: 04/19/2025] Open
Abstract
Cancer is a complex and highly lethal disease marked by unchecked cell proliferation, aggressive behavior, and a strong tendency to metastasize. Despite significant advancements in cancer diagnosis and treatment, challenges such as early detection difficulties, drug resistance, and adverse effects of radiotherapy or chemotherapy continue to threaten patient survival. MicroRNAs (miRNAs) have emerged as critical regulators in cancer biology, with miR-506 being extensively studied and recognized for its tumor-suppressive effects across multiple cancer types. This review examines the regulatory mechanisms of miR-506 in common cancers, focusing on its role in the competing endogenous RNA (ceRNA) network and its effects on cancer cell proliferation, apoptosis, and migration. We also discuss the potential of miR-506 as a therapeutic target and its role in overcoming drug resistance in cancer treatment. Overall, these insights underscore the therapeutic potential of miR-506 and its promise in developing novel cancer therapies.
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Affiliation(s)
- Shuzhen Mao
- Department of Pharmacy, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Junyan Li
- Department of Pathology, Second People’s Hospital of Ningyang, Taian, Shandong, China
| | - Jiahui Huang
- Jining Key Laboratory of Pharmacology, School of Basic Medicine, Jining Medical University, Jining, Shandong, China
| | - Lili Lv
- Department of Pathology, Second People’s Hospital of Ningyang, Taian, Shandong, China
| | - Qilian Zhang
- Department of Pathology, People’s Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Qing Cheng
- Jining Key Laboratory of Pharmacology, School of Basic Medicine, Jining Medical University, Jining, Shandong, China
| | - Xiaojing Liu
- Jining Key Laboratory of Pharmacology, School of Basic Medicine, Jining Medical University, Jining, Shandong, China
| | - Zhiwei Bi
- Jining Key Laboratory of Pharmacology, School of Basic Medicine, Jining Medical University, Jining, Shandong, China
| | - Jing Yao
- Jining Key Laboratory of Pharmacology, School of Basic Medicine, Jining Medical University, Jining, Shandong, China
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5
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Liu W, Wang W. LncRNA in gastric cancer drug resistance: deciphering the therapeutic strategies. Front Oncol 2025; 15:1552773. [PMID: 40236651 PMCID: PMC11996845 DOI: 10.3389/fonc.2025.1552773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 03/17/2025] [Indexed: 04/17/2025] Open
Abstract
Gastric cancer (GC) is an exceedingly aggressive disease and ranks as the third leading cause of cancer-related deaths, which poses a huge health burden globally. Chemotherapy is commonly employed during the middle to advanced stages of cancer, although it faces frequent treatment failures attributed to drug resistance. Thus, it is imperative for researchers to identify potential targets for overcoming therapeutic resistance, thereby facilitating the development of novel anti-cancer agents for GC patients with advanced stages. Long noncoding RNAs (lncRNAs) are a diverse group of transcripts with limited protein-coding capacity, which have been recognized for functional molecules for regulating cancer progression including cell proliferation, metastasis, and drug resistance in GC. In this review, we examine the intricate molecular networks on the role of lncRNAs in drug resistance of GC. LncRNAs conferred cancer cell resistance to anti-cancer drug through various molecular mechanisms, therefore functioning as promising therapeutic targets for GC patients. Additionally, we discuss current advancements of strategies targeting lncRNAs in cancer therapy, which may pave the way for lncRNA-mediated precision medicine for this malignant disease.
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Affiliation(s)
| | - WeiFa Wang
- Department of Gastrointestinal Surgery, Chengdu Seventh People’s Hospital, Chengdu, Sichuan, China
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Yu S, Liang J, Liu L, Chen M, Chen C, Zhou D. AC129507.1 is a ferroptosis-related target identified by a novel mitochondria-related lncRNA signature that is involved in the tumor immune microenvironment in gastric cancer. J Transl Med 2025; 23:290. [PMID: 40050892 PMCID: PMC11887229 DOI: 10.1186/s12967-025-06287-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 02/23/2025] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignancies. Previous studies have shown that mitochondrial metabolism is associated with malignancies. However, relevant research on mitochondria-related lncRNAs in GC is lacking. METHODS We integrated the corresponding information of patients with GC from The Cancer Genome Atlas (TCGA) database. Mitochondria-related lncRNAs were selected based on differential expression and a correlation analysis to construct a prognostic model. The mutation data were analyzed to distinguish differences in the tumor mutation burden (TMB). Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate immunological differences. A series of cell-based experiments were adopted to evaluate the biological behavior of GC. RESULTS A total of 1571 mitochondria-related lncRNAs were identified. A prognostic signature incorporating nine lncRNAs was built based on 293 suitable GC cases and could predict patient prognosis. The TMB and ssGSEA indicated that the low-risk group displayed increased immune function. The enrichment analysis indicated that the differentially expressed genes were enriched in metabolic functions. AC129507.1 was significantly upregulated in GC cells and associated with a poor prognosis, and its knockdown inhibited the proliferation and migration of GC cells. Mechanistically, silencing AC129507.1 led to abnormal glycolipid metabolism and oxidative stress, thus inducing ferroptosis. CONCLUSIONS Our nine-lncRNA risk signature could powerfully predict patient prognosis. AC129507.1 promoted the malignant phenotypes of GC cells. AC129507.1 could play a nonnegligible role in GC by promoting the formation of a immunosuppressive tumor microenvironment by inhibiting the initiation of ferroptosis, which needs to be further explored.
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Affiliation(s)
- Shanshan Yu
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Jinxiao Liang
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Lixiao Liu
- Department of Obstetrics and Gynecology, Ningbo City First Hospital, Ningbo University, Ningbo, China
| | - Ming Chen
- Department of Surgical Oncology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Cheng Chen
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China
| | - Donghui Zhou
- Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
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Zhang H, Tang H, Tu W, Peng F. Regulatory role of non-coding RNAs in 5-Fluorouracil resistance in gastrointestinal cancers. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2025; 8:4. [PMID: 39935428 PMCID: PMC11810461 DOI: 10.20517/cdr.2024.167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/29/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
Gastrointestinal (GI) cancers are becoming a growing cause of morbidity and mortality globally, posing a significant risk to human life and health. The main treatment for this kind of cancer is chemotherapy based on 5-fluorouracil (5-FU). However, the issue of 5-FU resistance is becoming increasingly prominent, which greatly limits its effectiveness in clinical treatment. Recently, numerous studies have disclosed that some non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), exert remarkable physiological functions within cells. In addition, these ncRNAs can also serve as important information communication molecules in the tumor microenvironment and regulate tumor chemotherapy resistance. In particular, they have been shown to play multiple roles in regulating 5-FU resistance in GI cancers. Herein, we summarize the targets, pathways, and mechanisms involved in regulating 5-FU resistance by ncRNAs and briefly discuss the application potential of ncRNAs as biomarkers or therapeutic targets for 5-FU resistance in GI cancers, aiming to offer a reference to tackle issues related to 5-FU resistance.
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Affiliation(s)
- Heng Zhang
- Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610051, Sichuan, China
- Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, Sichuan, China
| | - Hailin Tang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510700, Guangdong, China
| | - Wenling Tu
- Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, Sichuan, China
| | - Fu Peng
- Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610051, Sichuan, China
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu 610041, Sichuan, China
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8
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Yang TF, Li XR, Kong MW. Molecular mechanisms underlying roles of long non-coding RNA small nucleolar RNA host gene 16 in digestive system cancers. World J Gastrointest Oncol 2024; 16:4300-4308. [PMID: 39554746 PMCID: PMC11551640 DOI: 10.4251/wjgo.v16.i11.4300] [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: 02/25/2024] [Revised: 06/13/2024] [Accepted: 07/02/2024] [Indexed: 10/25/2024] Open
Abstract
This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors. The first study, by Zhao et al, explored how hBD-1 affects colon cancer, via the lncRNA TCONS_00014506, by inhibiting mTOR and promoting autophagy. The second one, by Li et al, identified the lncRNA prion protein testis specific (PRNT) as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance, suggesting PRNT as a potential therapeutic target for colorectal cancer. Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers. As a recent research hotspot, SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers. The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA, interacting with other proteins, regulating various genes, and affecting downstream target molecules. This review systematically examines the recently reported biological functions, related molecular mechanisms, and potential clinical significance of SNHG16 in various digestive system cancers, and explores the relationship between SNHG16 and digestive system cancers. The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.
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Affiliation(s)
- Ting-Fang Yang
- Department of Oncology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Xin-Rui Li
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Mo-Wei Kong
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
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Yu Q, Wu T, Xu W, Wei J, Zhao A, Wang M, Li M, Chi G. PTBP1 as a potential regulator of disease. Mol Cell Biochem 2024; 479:2875-2894. [PMID: 38129625 DOI: 10.1007/s11010-023-04905-x] [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: 07/10/2023] [Accepted: 11/16/2023] [Indexed: 12/23/2023]
Abstract
Polypyrimidine tract-binding protein 1 (PTBP1) is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which plays a key role in alternative splicing of precursor mRNA and RNA metabolism. PTBP1 is universally expressed in various tissues and binds to multiple downstream transcripts to interfere with physiological and pathological processes such as the tumor growth, body metabolism, cardiovascular homeostasis, and central nervous system damage, showing great prospects in many fields. The function of PTBP1 involves the regulation and interaction of various upstream molecules, including circular RNAs (circRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These regulatory systems are inseparable from the development and treatment of diseases. Here, we review the latest knowledge regarding the structure and molecular functions of PTBP1 and summarize its functions and mechanisms of PTBP1 in various diseases, including controversial studies. Furthermore, we recommend future studies on PTBP1 and discuss the prospects of targeting PTBP1 in new clinical therapeutic approaches.
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Affiliation(s)
- Qi Yu
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Tongtong Wu
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Wenhong Xu
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Junyuan Wei
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Anqi Zhao
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Miaomiao Wang
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China
| | - Meiying Li
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China.
| | - Guangfan Chi
- The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People's Republic of China.
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Khaleel AQ, Alshahrani MY, Rizaev JA, Malathi H, Devi S, Pramanik A, Mustafa YF, Hjazi A, Muazzamxon I, Husseen B. siRNA-based strategies to combat drug resistance in gastric cancer. Med Oncol 2024; 41:293. [PMID: 39428440 DOI: 10.1007/s12032-024-02528-w] [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: 08/17/2024] [Accepted: 09/27/2024] [Indexed: 10/22/2024]
Abstract
Chemotherapy is a key treatment option for gastric cancer, but over 50% of patients develop either inherent or acquired resistance to these drugs, resulting in a 5-year survival rate of only about 20%. The primary treatment for advanced gastric cancer typically involves chemotherapy based on platinum or fluorouracil. Several factors can contribute to platinum resistance, including decreased drug uptake, increased drug efflux or metabolism, enhanced DNA repair, activation of pro-survival pathways, and inhibition of pro-apoptotic pathways. In recent years, there has been significant progress in biology aimed at finding innovative and more effective methods to overcome chemotherapy resistance. Small interfering RNAs (siRNAs) have emerged as a significant advancement in gene expression regulation, showing promise in enhancing the sensitivity of gastric cancer cells to chemotherapy drugs. However, siRNA therapies still face major challenges, particularly in terms of stability and efficient delivery in vivo. This article discusses the advances in siRNA therapy and its potential role in overcoming resistance to chemotherapeutic drugs such as cisplatin, 5-FU, doxorubicin, and paclitaxel in the treatment of gastric cancer.
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Affiliation(s)
- Abdulrahman Qais Khaleel
- Department of Medical Instruments Engineering, College of Engineering, University of Al Maarif, Ramadi, Al Anbar, 31001, Iraq.
| | - Mohammad Y Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Jasur Alimdjanovich Rizaev
- Department of Public Health and Healthcare Management, Rector, Samarkand State Medical University, 18 Amir Temur Street, Samarkand, Uzbekistan.
| | - H Malathi
- Department of Biotechnology and Genetics, School of Sciences Jain (Deemed to be University), Bangalore, Karnataka, India
| | - Seema Devi
- Chandigarh Pharmacy College, Chandigarh Group of Colleges, Jhanjheri, Mohali, 140307, Punjab, India
| | - Atreyi Pramanik
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | - Ismoilova Muazzamxon
- Department of Propaedeutics of Internal Diseases, Fergana Medical Institute of Public Health, Fergana, Uzbekistan
- Western Caspian University, Scientific Researcher, Baku, Azerbaijan
| | - Beneen Husseen
- Medical Laboratory Technique College, the Islamic University, Najaf, Iraq
- Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical Laboratory Technique College, the Islamic University of Babylon, Babylon, Iraq
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11
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Vaghari-Tabari M, Qujeq D, Hashemzadeh MS. Long noncoding RNAs as potential targets for overcoming chemoresistance in upper gastrointestinal cancers. Biomed Pharmacother 2024; 179:117368. [PMID: 39214010 DOI: 10.1016/j.biopha.2024.117368] [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: 05/27/2024] [Revised: 08/16/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024] Open
Abstract
In the last decade, researchers have paid much attention to the role of noncoding RNA molecules in human diseases. Among the most important of these molecules are LncRNAs, which are RNA molecules with a length of more than 200 nucleotides. LncRNAs can regulate gene expression through various mechanisms, such as binding to DNA sequences and interacting with miRNAs. Studies have shown that LncRNAs may be valuable therapeutic targets in treating various cancers, including upper-gastrointestinal cancers. Upper gastrointestinal cancers, mainly referring to esophageal and gastric cancers, are among the deadliest gastrointestinal cancers. Despite notable advances, traditional chemotherapy remains a common strategy for treating these cancers. However, chemoresistance poses a significant obstacle to the effective treatment of upper gastrointestinal cancers, resulting in a low survival rate. Chemoresistance arises from various events, such as the enhancement of efflux and detoxification of chemotherapy agents, reduction of drug uptake, alteration of drug targeting, reduction of prodrug activation, strengthening of EMT and stemness, and the attenuation of apoptosis in cancerous cells. Tumor microenvironment also plays an important role in chemoresistance. Interestingly, a series of studies have revealed that LncRNAs can influence important mechanisms associated with some of the aforementioned events and may serve as promising targets for mitigating chemoresistance in upper gastrointestinal cancers. In this review paper, following a concise overview of chemoresistance mechanisms in upper gastrointestinal cancers, we will review the most intriguing findings of these investigations in detail.
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Affiliation(s)
- Mostafa Vaghari-Tabari
- Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
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Zhao L, Kan Y, Wang L, Pan J, Li Y, Zhu H, Yang Z, Xiao L, Fu X, Peng F, Ren H. Roles of long non‑coding RNA SNHG16 in human digestive system cancer (Review). Oncol Rep 2024; 52:106. [PMID: 38940337 PMCID: PMC11234248 DOI: 10.3892/or.2024.8765] [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: 05/23/2023] [Accepted: 04/26/2024] [Indexed: 06/29/2024] Open
Abstract
The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non‑coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.
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Affiliation(s)
- Lujie Zhao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yuling Kan
- Central Laboratory of Binzhou People's Hospital, Binzhou, Shandong 256600, P.R. China
| | - Lu Wang
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Jiquan Pan
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yun Li
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haiyan Zhu
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Zhongfa Yang
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Lin Xiao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Xinhua Fu
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Fujun Peng
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
- Weifang Key Laboratory of Collaborative Innovation of Intelligent Diagnosis and Treatment and Molecular Diseases, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haipeng Ren
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
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Ye H, Li MY, Shi RH. Advances in understanding of mechanism of long non-coding RNA SNHG16 in digestive system tumors. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:405-411. [DOI: 10.11569/wcjd.v32.i6.405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
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Meng X, Bai X, Ke A, Li K, Lei Y, Ding S, Dai D. Long Non-Coding RNAs in Drug Resistance of Gastric Cancer: Complex Mechanisms and Potential Clinical Applications. Biomolecules 2024; 14:608. [PMID: 38927012 PMCID: PMC11201466 DOI: 10.3390/biom14060608] [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: 03/10/2024] [Revised: 05/11/2024] [Accepted: 05/16/2024] [Indexed: 06/28/2024] Open
Abstract
Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent relapse and metastasis. The current treatment strategies have limited overall efficacy because of intrinsic or acquired drug resistance. Recent evidence suggests that dysregulated long non-coding RNAs (lncRNAs) play a significant role in mediating drug resistance in GC. Therefore, there is an imperative to explore novel molecular mechanisms underlying drug resistance in order to overcome this challenging issue. With advancements in deep transcriptome sequencing technology, lncRNAs-once considered transcriptional noise-have garnered widespread attention as potential regulators of carcinogenesis, including tumor cell proliferation, metastasis, and sensitivity to chemo- or radiotherapy through multiple regulatory mechanisms. In light of these findings, we aim to review the mechanisms by which lncRNAs contribute to drug therapy resistance in GC with the goal of providing new insights and breakthroughs toward overcoming this formidable obstacle.
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Affiliation(s)
- Xiangyu Meng
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
- Department of Gastric Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang 110042, China
| | - Xiao Bai
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Angting Ke
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Kaiqiang Li
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Yun Lei
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Siqi Ding
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
| | - Dongqiu Dai
- Department of Surgical Oncology, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China; (X.M.); (X.B.); (K.L.); (Y.L.); (S.D.)
- Cancer Center, the Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China
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Cheng T, Gu ML, Xu WQ, Ye DW, Zha ZY, Fang WG, Mao LK, Ning J, Hu XB, Ding YH. Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis. Heliyon 2024; 10:e30388. [PMID: 38756581 PMCID: PMC11096951 DOI: 10.1016/j.heliyon.2024.e30388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 04/24/2024] [Accepted: 04/25/2024] [Indexed: 05/18/2024] Open
Abstract
Objective This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.
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Affiliation(s)
- Tao Cheng
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Ming-Li Gu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Wei-Qiang Xu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Da-Wen Ye
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Ze-Yu Zha
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Wen-Ge Fang
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Li-Kai Mao
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Jing Ning
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Xing-Bang Hu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
| | - Yong-Hui Ding
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, China
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Shi Y, Adu-Amankwaah J, Zhao Q, Li X, Yu Q, Bushi A, Yuan J, Tan R. Long non-coding RNAs in drug resistance across the top five cancers: Update on their roles and mechanisms. Heliyon 2024; 10:e27207. [PMID: 38463803 PMCID: PMC10923722 DOI: 10.1016/j.heliyon.2024.e27207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Cancer drug resistance stands as a formidable obstacle in the relentless fight against the top five prevalent cancers: breast, lung, colorectal, prostate, and gastric cancers. These malignancies collectively account for a significant portion of cancer-related deaths worldwide. In recent years, long non-coding RNAs (lncRNAs) have emerged as pivotal players in the intricate landscape of cancer biology, and their roles in driving drug resistance are steadily coming to light. This comprehensive review seeks to underscore the paramount significance of lncRNAs in orchestrating resistance across a spectrum of different cancer drugs, including platinum drugs (DDP), tamoxifen, trastuzumab, 5-fluorouracil (5-FU), paclitaxel (PTX), and Androgen Deprivation Therapy (ADT) across the most prevalent types of cancer. It delves into the multifaceted mechanisms through which lncRNAs exert their influence on drug resistance, shedding light on their regulatory roles in various facets of cancer biology. A comprehensive understanding of these lncRNA-mediated mechanisms may pave the way for more effective and personalized treatment strategies, ultimately improving patient outcomes in these challenging malignancies.
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Affiliation(s)
- Yue Shi
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
| | - Joseph Adu-Amankwaah
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
| | - Qizhong Zhao
- Department of Emergency, The First Hospital of China Medical University, Shenyang, China
| | - Xin Li
- Clinical Medical College, Jining Medical University, 272067, Jining, China
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
| | - Qianxue Yu
- Clinical Medical College, Jining Medical University, 272067, Jining, China
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
| | - Aisha Bushi
- School of International Education, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Jinxiang Yuan
- Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, 272067, Jining, China
- Lin He's Academician Workstation of New Medicine and Clinical Translation, Jining Medical University, 272067, Jining, China
| | - Rubin Tan
- Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China
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Gao Q, Huang C, Liu T, Yang F, Chen Z, Sun L, Zhao Y, Wang M, Luo L, Zhou C, Zhu W. Gastric cancer mesenchymal stem cells promote tumor glycolysis and chemoresistance by regulating B7H3 in gastric cancer cells. J Cell Biochem 2024; 125:e30521. [PMID: 38226525 DOI: 10.1002/jcb.30521] [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: 10/06/2023] [Revised: 12/01/2023] [Accepted: 12/27/2023] [Indexed: 01/17/2024]
Abstract
Despite surgical treatment combined with multidrug therapy having made some progress, chemotherapy resistance is the main cause of recurrence and death of gastric cancer (GC). Gastric cancer mesenchymal stem cells (GCMSCs) have been reported to be correlated with the limited efficacy of chemotherapy in GC, but the mechanism of GCMSCs regulating GC resistance needs to be further studied. The gene set enrichment analysis (GSEA) was performed to explore the glycolysis-related pathways heterogeneity across different cell subpopulations. Glucose uptake and lactate production assays were used to evaluate the importance of B7H3 expression in GCMSCs-treated GC cells. The therapeutic efficacy of oxaliplatin (OXA) and paclitaxel (PTX) was determined using CCK-8 and colony formation assays. Signaling pathways altered by GCMSCs-CM were revealed by immunoblotting. The expression of TNF-α in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by western blot analysis and qPCR. Our results showed that the OXA and PTX resistance of GC cells were significantly enhanced in the GCMSCs-CM treated GC cells. Acquired OXA and PTX resistance was characterized by increased cell viability for OXA and PTX, the formation of cell colonies, and decreased levels of cell apoptosis, which were accompanied by reduced levels of cleaved caspase-3 and Bax expression, and increased levels of Bcl-2, HK2, MDR1, and B7H3 expression. Blocking TNF-α in GCMSCs-CM, B7H3 knockdown or the use of 2-DG, a key enzyme inhibitor of glycolysis in GC cells suppressed the OXA and PTX resistance of GC cells that had been treated with GCMSCs-CM. This study shows that GCMSCs-CM derived TNF-α could upregulate the expression of B7H3 of GC cells to promote tumor chemoresistance. Our results provide a new basis for the treatment of GC.
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Affiliation(s)
- Qiuzhi Gao
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Chao Huang
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Ting Liu
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Fumeng Yang
- Department of Laboratory Medicine, Lianyungang Clinical College of Jiangsu University, Lianyungang, Jiangsu, China
| | - Zhihong Chen
- Department of Gastrointestinal Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
| | - Li Sun
- Department of Clinical Laboratory, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
| | - Yuanyuan Zhao
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Mei Wang
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Liqi Luo
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Chenglin Zhou
- Department of Laboratory Medicine, Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, China
| | - Wei Zhu
- School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
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Luo Y, Lu X, Ma W, Xiao Y, Wei C, Yuan X, Wu Y, Wang Y, Xiong Y, Yu X, Wu X, He S, Liu Y, Wang J, Wu Q, Zhou H, Jiang Z. Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway. J Cell Mol Med 2023; 27:3591-3600. [PMID: 37621132 PMCID: PMC10660622 DOI: 10.1111/jcmm.17925] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 07/22/2023] [Accepted: 08/04/2023] [Indexed: 08/26/2023] Open
Abstract
Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.
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Affiliation(s)
- Yaomin Luo
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Xintong Lu
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Wenrong Ma
- School of PharmacyNorth Sichuan Medical CollegeNanchongChina
| | - Yang Xiao
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Chen Wei
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Xiaoxia Yuan
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- School of PharmacyNorth Sichuan Medical CollegeNanchongChina
| | - Yueyue Wu
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Yunlin Wang
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Yiman Xiong
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Xin Yu
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Xue Wu
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Siqi He
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Yayudie Liu
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Jinjing Wang
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
| | - Qing Wu
- Department of Rehabilitation Medicinethe Affiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Hui Zhou
- Department of Clinical Laboratorythe Affiliated Hospital of Jiaxing UniversityJiaxingChina
| | - Zhen Jiang
- Institute of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
- Department of Biochemistry and Molecular Biology, School of Basic Medicine and Forensic MedicineNorth Sichuan Medical CollegeNanchongChina
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Cai Y, Tian J, Su Y, Shi X. MiR-506 targets polypyrimidine tract-binding protein 1 to inhibit airway inflammatory response and remodeling via mediating Wnt/β-catenin signaling pathway. Allergol Immunopathol (Madr) 2023; 51:15-24. [PMID: 37169555 DOI: 10.15586/aei.v51i3.676] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 10/12/2022] [Indexed: 05/13/2023]
Abstract
BACKGROUND Airway remodeling, which contributes to the clinical course of childhood asthma, occurs due to airway inflammation and is featured by anomalous biological behaviors of airway smooth muscle cells (ASMCs). microRNA (miRNA) plays an essential role in the etiopathogenesis of asthma. OBJECTIVE This research was aimed to characterize miR-506 in asthma and uncover potential regulatory machinery. MATERIAL AND METHODS The asthmatic cell model was established by treating ASMCs with transforming growth factor-beta1 (TGF-β1) and assessed by the levels of interleukin (IL)-1β and interferon gamma (IFN-γ). Using real-time quantitative polymerase chain reaction, mRNA expression of miR-506 and polypyrimidine tract-binding protein 1 (PTBP1) was measured. Cell counting kit-8 and Transwell migration tests were used for estimating the capacity of ASMCs to proliferate and migrate. Luciferase reporter assay was used to corroborate whether miR-506 was directly bound to PTBP1. Expression of PTBP1, collagen I and III, and essential proteins of the wingless-related integration (Wnt)/β-catenin pathway (β-catenin, c-MYC and cyclin D1) was accomplished by Western blot analysis. The involvement of Wnt/β-catenin signaling in asthma was confirmed by Wnt signaling pathway inhibitor (IWR-1). RESULTS miR-506 was poorly expressed in asthmatic tissues and cell model. Functionally, overexpression of miR-506 reduced aberrant proliferation, migration, inflammation and collagen deposition of ASMCs triggered by TGF-β1. Mechanically, miR-506 directly targeted the 3' untranslated region (3-UTR) of PTBP1 and had a negative regulation on PTBP1 expression. Moreover, overexpression of miR-506 suppressed the induction of Wnt/β-catenin pathway. The administration of IWR-1 further validated negative correlation between miR-506 and the Wnt/β-catenin pathway in asthma. CONCLUSION Our data indicated that targeting miR-506/PTBP1/Wnt/β-catenin axis might point in a helpful direction for treating asthma in children.
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Affiliation(s)
- Yuxiang Cai
- Department of Emergency, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Jifeng Tian
- Department of Integrated Traditional Chinese and Western Medicine, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Yufei Su
- Department of Emergency, Xi'an Children's Hospital, Xi'an, Shaanxi, China
| | - Xiaolan Shi
- Department of Respiratory Asthma Center, Xi'an Children's Hospital, Xi'an, Shaanxi, China;
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