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Wei X, Jiang Y, Yang G, Chang T, Sun G, Chen S, Wu S, Liu R. MicroRNA-367-3p directly targets RAB23 and inhibits proliferation, migration and invasion of bladder cancer cells and increases cisplatin sensitivity. J Cancer Res Clin Oncol 2023; 149:17807-17821. [PMID: 37935937 PMCID: PMC10725407 DOI: 10.1007/s00432-023-05484-6] [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: 07/18/2023] [Accepted: 10/18/2023] [Indexed: 11/09/2023]
Abstract
OBJECTIVES This study investigated the biological role of miR-367-3p upregulation in bladder cancer and verified the mutual relation between miR-367-3p and RAB23. MATERIALS AND METHODS Expression levels of miR-367-3p were determined by RT-qPCR in bladder cancer cell lines and human bladder cancer tissues. The effects of miR-367-3p on proliferation, migration and invasion were evaluated by cell colony formation assays, wound healing assays and trans-well assays, respectively. The effects of miR-367-3p and RAB23 on cisplatin sensitivity of bladder cancer cells were assessed by CCK-8 assay. The expression of its target-RAB23 was determined by western blotting in T24, 5637. Plasmids used in dual-luciferase assays were constructed to confirm the action of miR-367-3p on downstream target-RAB23 in T24 cells. And also, the role of miR-367-3p in tumorigenesis was also confirmed in nude mouse models. RESULTS The downregulation of miR-367-3p was observed in human bladder cancer tissues. MiR-367-3p downregulation positively correlated with tumor stage and tumor grade. MiR-367-3p overexpression in T24, 5637 cells suppressed the proliferation, migration, and invasion of bladder cancer cells in vitro while decreasing IC50 values under T24 and 5637 cisplatin treatment conditions. RAB23 was shown to be upregulated in bladder cancer tissues and cell lines. MiR-367-3p directly bound to the 3' UTR of RAB23 in T24 cells. RAB23 was potentially accounted for the aforementioned functions of miR-367-3p. Tumor formation experiments in nude mouse models confirmed that overexpression of miR-367-3p could inhibit tumor growth and invasion in vivo. CONCLUSIONS miR-367-3p acts as a tumor suppressor in bladder cancer by downregulating RAB23 signaling. We conjecture that miR-367-3p-mediated downregulation of RAB23 expression may be a new therapeutic strategy for bladder cancer treatment.
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Affiliation(s)
- Xifeng Wei
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
- Department of Urology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Yuchen Jiang
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Guanghua Yang
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Taihao Chang
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Guangyu Sun
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Shuaiqi Chen
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Shangrong Wu
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China
| | - Ranlu Liu
- Department of Urology, The Second Hospital of Tianjin Medical University & Tianjin Institute of Urology, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China.
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Expression analysis of circulating miR-22, miR-122, miR-217 and miR-367 as promising biomarkers of acute lymphoblastic leukemia. Mol Biol Rep 2023; 50:255-265. [PMID: 36327023 DOI: 10.1007/s11033-022-08016-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 10/07/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND The role of serum-based biomarkers such as microRNAs in cancer diagnosis has been extensively established. This study aimed to determine the expression levels of bioinformatically selected miRNAs and whether they can be used as biomarkers or a new therapeutic target in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS The expression levels of serum miR-22, miR-122, miR-217, and miR-367 in 21 ALL patients and 21 healthy controls were measured using quantitative real-time PCR. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) was used to assess candidate miRNAs' diagnostic value as a biomarker. RESULTS The results showed that miR-217 was markedly decreased in patients with ALL compared to controls. Moreover, miR-22, miR-122, and miR-367 were found to be upregulated. Furthermore, ROC analysis showed that serum miR-217 and miR-367 could differentiate ALL patients from healthy individuals, while miR-22 has approximate discriminatory power that requires further investigation. CONCLUSION These results provide promising preliminary evidence that circulating miR-217 and miR-367 could be considered potent diagnostic biomarkers and therapeutic goals in this disease.
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3
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He L, Pan X, Wang X, Cao Y, Chen P, Du C, Huang D. Rab6c is a new target of miR‑218 that can promote the progression of bladder cancer. Mol Med Rep 2021; 24:792. [PMID: 34515321 DOI: 10.3892/mmr.2021.12432] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 07/08/2021] [Indexed: 11/05/2022] Open
Abstract
Bladder cancer has high morbidity and mortality rates among the male genitourinary system tumor types. MicroRNA‑218 (miR‑218) is associated with the development of a variety of cancer types, including bladder cancer. Rab6c is a member of the Rab family and is involved in drug resistance in MCF7 cells. The aim of the present study was to clarify the relationship between Rab6c and miR‑218 in bladder cancer cell lines. In this study, the expression levels of miR‑218 and Rab6c were evaluated via reverse transcription‑quantitative PCR and western blotting, respectively. The association between Rab6c and miR‑218 was recognized via TargetScan analysis and dual luciferase reporter gene detection. Cell proliferation was analyzed using Cell Counting Kit‑8 and colony formation assays, and the invasive ability was measured via Transwell assays. Rab6c was highly expressed in bladder cancer, while miR‑218 had abnormally low expression in bladder cancer. In addition, there was a mutual regulation between Rab6c and miR‑218 in bladder cancer. It was found that overexpression of Rab6c significantly enhanced the proliferation, colony formation and invasion of T24 and EJ cells. Furthermore, miR‑218 overexpression blocked the promoting effects of Rab6c on the malignant behavior of bladder cancer cells. Thus, Rab6c promotes the proliferation and invasion of bladder cancer cells, while miR‑218 has the opposite effect, which may provide a novel insight for the treatment of bladder cancer.
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Affiliation(s)
- Long He
- Department of Urology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225003, P.R. China
| | - Xiang Pan
- Department of Urology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225003, P.R. China
| | - Xialu Wang
- Key Laboratory of Pattern Recognition in Liaoning, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China
| | - Yuhua Cao
- Department of The Second Cadre Ward, General Hospital of Northern Theater Command, National Center for Clinical Research of Geriatric Diseases, Shenyang, Liaoning 157099, P.R. China
| | - Peng Chen
- Department of Urology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110013, P.R. China
| | - Cheng Du
- Department of Oncology, General Hospital of Northern Theater Command, Shenyang, Liaoning 110013, P.R. China
| | - Daifa Huang
- Department of The Second Cadre Ward, General Hospital of Northern Theater Command, National Center for Clinical Research of Geriatric Diseases, Shenyang, Liaoning 157099, P.R. China
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4
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Du W, Li D, Xie J, Tang P. miR‑367‑3p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells. Oncol Rep 2021; 46:192. [PMID: 34278506 PMCID: PMC8299014 DOI: 10.3892/or.2021.8143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 04/02/2021] [Indexed: 12/13/2022] Open
Abstract
MicroRNAs play an important role in tumor cell proliferation, invasion, and Rab23 is a member of the Ras-related small GTPase family and plays a critical role in the progression of may types of tumors. The present study was designed to investigate the inhibitory effect of microRNA (miR)-367-3p on the proliferation, invasion, and metastasis of prostate cancer cells. qRT-PCR was used to detect the expression of miR-367-3p in prostate cancer and adjacent tissues. Cell proliferation, scratch, and Transwell assays were performed to verify the inhibitory effect of miR-367-3p overexpression or Ras-related protein Rab 23 (Rab23) knockdown on prostate cancer. Double luciferase reporter assay was utilized to verify whether miR-367-3p could target the Rab23 3′-untranslated region (UTR). The expression levels of Rab23, Gli1, and Gli2 in prostate cancer cells transfected with the miR-367-3p mimic were detected via qRT-PCR analysis. miR-367-3p expression in the prostate cancer tissues was downregulated compared with that in the para-cancer control tissues. miR-367-3p expression in DU145 and PC3 cells was also downregulated compared with that in the human prostate epithelial cell line RWPE-1. The overexpression of miR-367-3p or the knockdown of Rab23 inhibited the proliferation, invasion, and metastasis of prostate cancer cells. The results of the luciferase reporter assay confirmed that Rab23 was a target gene that was regulated by miR-367-3p. miR-367-3p specifically bound to the 3′-UTR of Rab23 mRNA. The overexpression of miR-367-3p inhibited Rab23 expression and the Hedgehog pathway. Cell function experiments confirmed that the overexpression of Rab23 reversed the anticancer effect of miR-367-3p. miR-367-3p was able to inhibit the Hedgehog pathway by targeting the expression of the Rab23 gene, thus inhibiting the proliferation, invasion, and metastasis of prostate cancer cells.
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Affiliation(s)
- Wei Du
- Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Dong Li
- Department of Urology, Nanhai Hospital of Guangdong Provincial People's Hospital, Foshan, Guangdong 528251, P.R. China
| | - Jianhao Xie
- Department of Clinical Laboratory, Nanhai Hospital of Guangdong Provincial People's Hospital, Foshan, Guangdong 528251, P.R. China
| | - Ping Tang
- Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
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Liu B, Pan J, Fu C. Correlation of microRNA-367 in the clinicopathologic features and prognosis of breast cancer patients. Medicine (Baltimore) 2021; 100:e26103. [PMID: 34087856 PMCID: PMC8183767 DOI: 10.1097/md.0000000000026103] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 05/06/2021] [Indexed: 01/04/2023] Open
Abstract
Breast cancer (BC) is a malignant tumor originating from cells of the breast. Notably, microRNAs have been recognized as biomarkers of BC metastasis. The present study is designed to evaluate the association between microRNA (miR)-367 expression and BC with the variance of clinicopathologic features and prognosis.Initially, 63 BC patients were allocated in the BC group, while the other 40 healthy volunteers were recruited as the control group. miR-367 expression in the serum of patients and healthy controls was detected using real-time polymerase chain reaction. Furthermore, the relation between miR-367 in serum and clinicopathologic features and prognosis of BC patients was accessed.miR-367 expression in serum of the BC group was evidently lower than that in the control group (all P < .001). Besides, miR-367 underexpression in the BC group was closely associated with the variance in tumor nodes metastasis advanced stage, tumor diameter, and lymph node metastasis of BC (all P < .001). In addition, compared with the control group, poorly expressed miR-367 BC group had short period of disease-free survival and overall survival (all P < .001).Our study demonstrated that miR-367 expression is associated with BC clinicopathologic features and prognosis. This investigation may offer new insight for BC treatment.
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6
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MicroRNA-367 directly targets PIK3R3 to inhibit proliferation and invasion of oral carcinoma cells. Biosci Rep 2021; 40:223849. [PMID: 32378714 PMCID: PMC7260354 DOI: 10.1042/bsr20193867] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 04/07/2020] [Accepted: 04/08/2020] [Indexed: 12/13/2022] Open
Abstract
Recently, microRNA-367 (miR-367) has been reported to function as both tumor suppressor and oncogene in several cancer types, including gastric cancer, hepatocellular cancer and lung cancer. However, the biological function of miR-367 and its precise mechanisms in oral squamous cell carcinoma (OSCC) have not been well clarified. The aim of the present study was to study the roles of miR-367/PIK3R3 axis in OSCC. The levels of PIK3R3 and miR-367 were detected by quantitative PCR assay in OSCC tissues and cell lines. Moreover, the biological roles of miR-367 and PIK3R3 in OSCC cells were assessed by cell proliferation and invasion. The mRNA and protein levels of PIK3R3 were determined by using quantitative PCR and Western blotting assays. Luciferase assays were used to confirm that PIK3R3 was one target of miR-367. In the present study, the miR-367 level was dramatically reduced in OSCC tissues and cell lines, and the PIK3R3 expression was significantly enhanced. What’s more, the PIK3R3 expression was negatively related to the miR-367 level in OSCC tissues. Furthermore, up-regulation of miR-367 obviously restrained OSCC cells proliferation and invasion. We confirmed that miR-367 could directly target PIK3R3 by luciferase reporter assay. Besides, knockdown of PIK3R3 also could markedly inhibit the proliferation and invasion of OSCC cells. Finally, overexpression of miR-367 in OSCC cells partially reversed the promoted effects of PIK3R3 up-regulation. Overexpression of miR-367 restrained OSCC cells proliferation and invasion via regulation of PIK3R3.
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Raikundalia S, Sa'Dom SAFM, Few LL, Too WCS. MicroRNA-367-3p induces apoptosis and suppresses migration of MCF-7 cells by downregulating the expression of human choline kinase α. Oncol Lett 2021; 21:183. [PMID: 33574922 PMCID: PMC7816280 DOI: 10.3892/ol.2021.12444] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 11/16/2020] [Indexed: 12/11/2022] Open
Abstract
Choline kinase (ChK) catalyzes the first step in the CDP-choline pathway for the synthesis of phosphatidylcholine. The α isoform of this enzyme is overexpressed in various types of cancer and its inhibition or downregulation has been applied as an anticancer strategy. In spite of increasing attention being paid to ChK expression, as well as its activity and inhibition in cancer, there are only limited studies available on the regulation of ChK, including its regulation by microRNAs (miRNAs/miRs). The dysregulation of gene expression by miRNAs is a common cause for carcinogenesis. In the present study, miR-367-3p was predicted to target the 3′-untranslated region (UTR) of the ChK α (chka) mRNA transcript. The binding of miR-367-3p to the 3′-UTR of chka was validated by a luciferase assay. The effects of the miR-367-3p mimic on chka gene and protein expression levels were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. miR-367-3p significantly downregulated the expression of chka to ~60% of the negative control. Cells transfected with miR-367-3p exhibited higher levels of apoptosis and a lower cell migration compared with the control. To the best of our knowledge, the present study provided the first experimental evidence of the regulation of chka expression by miR-367-3p. The pro-apoptotic and suppressive effects of miR-367-3p on cell migration were similar to the anticancer effects resulting from the inhibition of ChK enzyme activity or the knockdown of chka gene expression by small interfering RNA. Therefore, these findings may potentially lead to the use of miR-367-3p in anticancer strategies that target ChK.
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Affiliation(s)
- Sweta Raikundalia
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | | | - Ling Ling Few
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
| | - Wei Cun See Too
- School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
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8
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Tao Y, Wan X, Fan Q, Wang Y, Sun H, Ma L, Sun C, Wu Y. Long non-coding RNA OIP5-AS1 promotes the growth of gastric cancer through the miR-367-3p/HMGA2 axis. Dig Liver Dis 2020; 52:773-779. [PMID: 31959478 DOI: 10.1016/j.dld.2019.11.017] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 11/22/2019] [Accepted: 11/27/2019] [Indexed: 12/11/2022]
Abstract
Increasing evidence shows that aberrant lncRNAs expression contributes to the progression of gastric cancer (GC). The role of the novel lncRNA OIP5-AS1 and its underlying mechanisms in the growth of GC is largely unknown. Here we demonstrate for the first time that OIP5-AS1 expression was up-regulated in GC tissues and cell lines, which significantly correlated with unfavorable clinical characteristics and shorter survival. The results of in vitro and in vivo gain- and loss-of-function experiments indicate that OIP5-AS1 promoted cell proliferation and colony formation while inhibiting apoptosis of GC cells. OIP5-AS1 functioned as an endogenous sponge for miR-367-3p in GC cells. Restoration of miR-367-3p expression abolished the biological effects of OIP5-AS1 on GC cells. Moreover, we show that HMGA2 was a downstream target of miR-367-3p and mediated the effects of OIP5-AS1 on GC cells. OIP5-AS1 regulated the activities of the PI3K/AKT and Wnt/β-catenin pathways through HMGA2. In conclusion, OIP5-AS1 functions as an oncogenic lncRNA that promotes the progression of GC and may serve as a therapeutic target for managing GC.
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Affiliation(s)
- Youmao Tao
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
| | - Xiaoyu Wan
- Department of Thyroid & Breast Surgery, The Second Hospital of Jilin University, Changchun, Jilin Province, China
| | - Qihao Fan
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yannan Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
| | - Haojie Sun
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
| | - Lushun Ma
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
| | - Caixia Sun
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
| | - Yuanyu Wu
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China.
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9
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Tabet F, Lee S, Zhu W, Levin MG, Toth CL, Cuesta Torres LF, Vinh A, Kim HA, Chu HX, Evans MA, Kuzmich ME, Drummond GR, Remaley AT, Rye KA, Sobey CG, Vickers KC. microRNA-367-3p regulation of GPRC5A is suppressed in ischemic stroke. J Cereb Blood Flow Metab 2020; 40:1300-1315. [PMID: 31296130 PMCID: PMC7238381 DOI: 10.1177/0271678x19858637] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Ischemic stroke is a major cause of mortality and long-term disability with limited treatment options, and a greater understanding of the gene regulatory mechanisms underlying ischemic stroke-associated neuroinflammation is required for new therapies. To study ischemic stroke in vivo, mice were subjected to sustained ischemia by intraluminal filament-induced middle cerebral artery occlusion (MCAo) for 24 h without reperfusion or transient ischemia for 30 min followed by 23.5 h reperfusion, and brain miRNA and mRNA expression changes were quantified by TaqMan OpenArrays and gene (mRNA) expression arrays, respectively. Sustained ischemia resulted in 18 significantly altered miRNAs and 392 altered mRNAs in mouse brains compared to Sham controls; however, the transient ischemic condition was found to impact only 6 miRNAs and 126 mRNAs. miR-367-3p was found to be significantly decreased in brain homogenates with sustained ischemia. G protein-coupled receptor, family C, group 5, member A (Gprc5a), a miR-367-3p target gene, was found to be significantly increased with sustained ischemia. In primary neurons, inhibition of endogenous miR-367-3p resulted in a significant increase in Gprc5a expression. Moreover, miR-367-3p was found to be co-expressed with GPRC5A in human neurons. Results suggest that loss of miR-367-3p suppression of GPRC5A may contribute to neuroinflammation associated with ischemic stroke.
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Affiliation(s)
- Fatiha Tabet
- Mechanisms of Disease and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Seyoung Lee
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia
| | - Wanying Zhu
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael G Levin
- National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Cynthia L Toth
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Luisa F Cuesta Torres
- Mechanisms of Disease and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Antony Vinh
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia
| | - Hyun Ah Kim
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia
| | - Hannah X Chu
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia
| | - Megan A Evans
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia
| | - Meaghan E Kuzmich
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Grant R Drummond
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia
| | - Alan T Remaley
- National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Kerry-Anne Rye
- Mechanisms of Disease and Translational Research, School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Christopher G Sobey
- Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.,Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria, Australia
| | - Kasey C Vickers
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
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10
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Chen H, Pan D, Yang Z, Li L. Integrated analysis and knockdown of RAB23 indicate the role of RAB23 in gastric adenocarcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 7:745. [PMID: 32042761 DOI: 10.21037/atm.2019.11.130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background The present study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) in gastric adenocarcinoma. Methods We performed integrated analysis to determine DEGs and DEmiRNAs of gastric adenocarcinoma based on the GEO database. A DEmiRNA-target interaction network was established. GO and KEGG pathway enrichment analyses were utilized. Then, MKN45 cells were transfected with shRNA-RAB23 to knock down the expression of RAB23. CCK-8, transwell and flow cytometry assays were utilized to measure the capacities for cell proliferation, migration and apoptosis, and the apoptosis-related gene and protein levels were measured by using polymerase chain reaction (PCR) and Western blot, respectively. Colocalization analysis of Snc1 with the vesicular protein VAMP3 and the endoplasmic reticulum protein Calnexin was performed to assess the influence of RAB23 on vesicle transport. Finally, we performed metabolomic analysis by using gas chromatography mass spectrometry (GC-MS). Results We performed MMIA of gastric adenocarcinoma based on two miRNA datasets and two mRNA datasets. A total of 4,586 DEmRNAs and 30 DEmiRNAs were obtained. The DEmRNAs of gastric adenocarcinoma were significantly enriched in PI3K/Akt signaling. We identified three interactions, hsa-miR-23a-3p-PTPN4, hsa-miR-20b-5p (hsa-miR-130a-3p)-TNFRSF10B, and hsa-miR-130a-3p (hsa-miR-363-3p)-RAB23, that may be related to the pathogenesis of gastric adenocarcinoma. The growth of MKN45 cells was inhibited by RAB23 knockdown via shRNA-RAB23 transfection. Metabolic analysis of three groups revealed a number of significantly altered metabolites, including glycerol, niacinamide, and nonadecanoic acid methylester. Conclusions RAB23 might be a target gene of hsa-miR-130a-3p and hsa-miR-363-3p. In gastric adenocarcinoma cells, knockdown of RAB23 inhibited cell proliferation, migration, and invasion and increased apoptosis by downregulating the PI3K/Akt pathway.
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Affiliation(s)
- Hui Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China
| | - Dun Pan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China
| | - Zhihuang Yang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China
| | - Liangqing Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350000, China
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11
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Yang T, Tian S, Wang L, Wang Y, Zhao J. MicroRNA-367-3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5-mediated Wnt/β-catenin signalling. Clin Exp Pharmacol Physiol 2019; 47:687-695. [PMID: 31792998 DOI: 10.1111/1440-1681.13222] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/30/2019] [Accepted: 11/29/2019] [Indexed: 12/16/2022]
Abstract
MicroRNA-367-3p (miR-367-3p) has been previously reported as a cancer-related miRNA that is dysregulated in various cancer types and functions either as an oncogenic or as tumour suppressive miRNA. However, whether miR-367-3p is dysregulated in cervical cancer and, further, whether it contributes to the development and progression of the disease remains unknown. Here, our results demonstrated that miR-367-3p expression was markedly decreased in both cervical cancer tissues and cell lines compared with corresponding controls. In vitro experiments revealed that miR-367-3p overexpression repressed the proliferation and invasion of cervical cancer cells. Notably, sperm-associated antigen 5 (SPAG5) was identified as a target gene of miR-367-3p. Moreover, decreased expression of miR-367-3p was correlated with high expression of SPAG5 in cervical cancer tissue specimens. SPAG5 inhibition or miR-367-3p overexpression significantly downregulated Wnt/β-catenin signalling in cervical cancer cells. However, the antitumour effect mediated by miR-367-3p overexpression was partially reversed by SPAG5 overexpression. Overall, these findings demonstrate that miR-367-3p overexpression restricts the proliferation and invasion of cervical cancer cells through targeting SPAG5 to downregulate Wnt/β-catenin signalling, suggesting a mechanism for the tumour suppressive function of miR-367-3p in cervical cancer. Our study highlights the involvement of miR-367-3p/SPAG5/Wnt/β-catenin signalling axis in regulating the malignant progression of cervical cancer.
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Affiliation(s)
- Ting Yang
- Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China
| | - Sijuan Tian
- Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China
| | - Linlin Wang
- Obstetrics and Gynecology Department, Ningbo First Hospital, Ningbo, China
| | - Yaohui Wang
- Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China
| | - Juan Zhao
- Obstetrics and Gynecology Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China
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12
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Yan L, Wu K, Du F, Yin X, Guan H. miR-384 suppressed renal cell carcinoma cell proliferation and migration through targeting RAB23. J Cell Biochem 2019; 120:1420-1426. [PMID: 30390327 DOI: 10.1002/jcb.27180] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 05/24/2018] [Indexed: 01/24/2023]
Abstract
microRNAs (miRNAs) are noncoding, short, and endogenous RNAs that play crucial roles in tumor progression at the post-transcriptional level. Here, we studied the role of miR-384 in the pathogenesis of renal cell carcinoma (RCC). We demonstrated that miR-384 expression was downregulated in the RCC specimens compared with nontumor specimens. Moreover, we showed that RAB23 expression was upregulated in the RCC tissues compared with nontumor tissues. Furthermore, we demonstrated that low expression of miR-384 was correlated with high levels of RAB23 in RCC tissues. We also demonstrated that the RAB23 was a direct target gene of miR-384 in RCC cells. In addition, overexpression of miR-384 suppressed RCC cell proliferation, cell cycle, and cell migration. Furthermore, ectopic expression of RAB23 promoted RCC cell proliferation, cell cycle, and cell migration. These data suggested that miR-384 played a tumor suppressor microRNA in the development of RCC partly through inhibiting RAB23 expression.
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Affiliation(s)
- Lihua Yan
- Department of Medical Oncology, Nanyang Second People's Hospital, Nanyang, Henan, China
| | - Kunxiang Wu
- Department of Orthopaedic Surgery, Nanyang Second People's Hospital, Nanyang, Henan, China
| | - Feng Du
- Department of Medical Oncology, Nanyang Second People's Hospital, Nanyang, Henan, China
| | - Xianzhe Yin
- Department of Medical Oncology, Nanyang Second People's Hospital, Nanyang, Henan, China
| | - Hongmei Guan
- Department of Medical Oncology, Nanyang Second People's Hospital, Nanyang, Henan, China
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13
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Shahabi A, Naghili B, Ansarin K, Zarghami N. The relationship between microRNAs and Rab family GTPases in human cancers. J Cell Physiol 2019; 234:12341-12352. [PMID: 30609026 DOI: 10.1002/jcp.28038] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 11/30/2018] [Indexed: 12/13/2022]
Abstract
microRNAs (miRNAs), as a group of noncoding RNAs, posttranscriptionally control gene expression by binding to 3'-untranslated region (3'-UTR). Ras-associated binding (Rab) proteins function as molecular switches for regulating vesicular transport, which mainly have oncogenic roles in cancer development and preventing the efficacy of chemotherapies. Increased evidence supported that miRNAs/Rabs interaction have been determined as potential therapeutics for cancer therapy. Nevertheless, instability and cross-targeting of miRNAs are main limitations of using miRNA-based therapeutic. The mutual interplay between Rabs and miRNAs has been poorly understood. In the present review, we focused on the essence and activity of these molecules in cancer pathogenesis. Also, numerous hindrances and potential methods in the expansion of miRNA as an anticancer therapeutics are mentioned.
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Affiliation(s)
- Arman Shahabi
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behrooz Naghili
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khalil Ansarin
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nosratollah Zarghami
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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14
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Rab34 regulates adhesion, migration, and invasion of breast cancer cells. Oncogene 2018; 37:3698-3714. [PMID: 29622794 DOI: 10.1038/s41388-018-0202-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 01/07/2018] [Accepted: 02/03/2018] [Indexed: 02/06/2023]
Abstract
The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion, and macropinocytosis. In this study, we found that Rab34 is over-expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion, and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin β3, and depletion of Rab34 promotes the degradation of integrin β3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase. Accordingly, Rab34 is tyrosine phosphorylated by Src at Y247 residue. A mutant mimicking phosphorylated form of Rab34 (Rab34Y247D) promotes cell migration and invasion. Importantly, the tyrosine phosphorylation of Rab34 is inhibited in cells in suspension, and increased with the cells re-adhesion. In addition, Rab34Y247D promotes cell adhesion, and enhances integrin β3 endocytosis and recycling. The results uncover a role of Rab34 in migration and invasion of breast cancer cells and its involvement in cancer metastasis, and provide a novel mechanism of tyrosine phosphorylation of Rab34 in regulating cell migration, invasion, and adhesion through modulating the endocytosis, stability, and recycling of integrin β3.
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15
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Long J, Luo J, Yin X. miR‑367 enhances the proliferation and invasion of cutaneous malignant melanoma by regulating phosphatase and tensin homolog expression. Mol Med Rep 2018; 17:6526-6532. [PMID: 29512776 PMCID: PMC5928632 DOI: 10.3892/mmr.2018.8663] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 01/17/2018] [Indexed: 12/11/2022] Open
Abstract
Melanoma presents a serious threat to human health but the underlying mechanisms have not been fully identified. Increasing evidence indicates that microRNAs exert a significant influence on the tumorigenesis and metastasis of different types of cancer. The present study aimed to identify the role of microRNA (miR)‑367 in the initiation and progression of melanoma and investigate its potential target. A total of 50 melanoma samples and 25 benign nevi tissues were used in the present study. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to determine the expression of mRNA and protein, respectively. Cell proliferation and invasion were assessed by CCK‑8, wound healing and Transwell assays. A proposed target mRNA of miR‑367 was determined using a luciferase reporter assay and an in vivo xenograft model was used to evaluate the function of miR‑367 in the progression of melanoma. It was revealed that miR‑367 was overexpressed in melanoma tissues and cell lines. The miR‑367 level in tumor tissues was positively correlated with tumor thickness, tumor stage, lymph node involvement, distant metastasis and the patient survival rate. A high miR‑367 level was observed to enhance the growth, migration and invasion of melanoma cells. Conversely, low miR‑367 levels suppressed the proliferation and invasion of melanoma cells. Furthermore, miR‑367 was revealed to bind directly to phosphatase and tensin homolog (PTEN) mRNA and regulate the expression of the PTEN protein. miR‑367 markedly increased the growth and invasion of melanoma cells, whereas the cotransfection of PTEN vectors limited the promoting function of miR‑367 in the proliferation and invasion of A375 cells. The upregulation of miR‑367 promoted tumor growth in vivo. In conclusion, the results revealed that miR‑367 serves a positive role in the development of melanoma and may be an important target for the treatment of cutaneous melanoma.
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Affiliation(s)
- Jianwen Long
- Department of Dermatology, The First Clinical School, Hubei University of Chinese Medicine, Wuhan, Hubei 430061, P.R. China
| | - Jing Luo
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, P.R. China
| | - Xuwen Yin
- Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430061, P.R. China
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16
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Liu X, Zheng J, Xue Y, Yu H, Gong W, Wang P, Li Z, Liu Y. PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells. Am J Cancer Res 2018; 8:1084-1105. [PMID: 29464001 PMCID: PMC5817112 DOI: 10.7150/thno.21740] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 11/02/2017] [Indexed: 12/26/2022] Open
Abstract
Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA molecules that function by binding to the Argonaute protein family (i.e., the PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in several cancers. However, the detailed roles of ncRNAs in glioma remain unclear. Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4 were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop was evaluated in cell and animal models. The association of the above molecules was analyzed. Results: Over-expression of PIWIL3, piR-30188 and miR-367-3p or knockdown of OIP5-AS1 resulted in inhibition of glioma cells progression. Binding sites between piR-30188 and OIP5-AS1 as well as between OIP5-AS1 and miR-367-3p were confirmed by RNA immunoprecipitation and luciferase assays. OIP5-AS1 knockdown or miR-367-3p over-expression contributed to a decrease in CEBPA (CCAAT/enhancer binding protein alpha) protein. Furthermore, CEBPA was detected as a target of miR-367-3p and played an oncogenic role in glioma. Treatment with CEBPA and miR-367-3p resulted in the modulation of downstream TRAF4 (TNF receptor-associated factor 4). PIWIL3 was also a target of CEBPA, forming a positive feedback loop in the growth regulation of glioma cells. Significantly, knockdown of OIP5-AS1 combined with over-expression of PIWIL3 and miR-367-3p resulted in tumor regression and extended survival in vivo. Conclusion: These results identified a novel molecular pathway in glioma cells that may provide a potential innovative approach for tumor therapy.
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17
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Xue H, Tian GY. MiR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23. Arch Biochem Biophys 2017; 637:48-55. [PMID: 29191386 DOI: 10.1016/j.abb.2017.11.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 11/07/2017] [Accepted: 11/26/2017] [Indexed: 12/17/2022]
Abstract
Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells. After being transfected with miR-429 mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further verified that the function of miR-429 in HCC cells was exerted through targeting RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might be a potential target for HCC treatment.
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Affiliation(s)
- Hongyan Xue
- Department of Pathology, Jinhua People's Hospital, Jinhua City, Zhejiang Province, 321000, China
| | - Guo-Yan Tian
- Department of Oncology and Hematology, The Affiliated Hospital of Hangzhou Normal University, No.126, Wenzhou Street, Gongshu District, Hangzhou City, Zhejiang Province, 310015, China.
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18
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Cai W, Jiang H, Yu Y, Xu Y, Zuo W, Wang S, Su Z. RETRACTED: miR-367 regulation of DOC-2/DAB2 interactive protein promotes proliferation, migration and invasion of osteosarcoma cells. Biomed Pharmacother 2017; 95:120-128. [PMID: 28837878 DOI: 10.1016/j.biopha.2017.07.158] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 07/13/2017] [Accepted: 07/30/2017] [Indexed: 02/03/2023] Open
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors, who have informed the Editor-in-Chief that miR-367 overexpression did not significantly reduce the DAB2IP level in MG-63 cells as shown in Figures 4C and 4D of the published article. Furthermore, the effects of miR-367 overexpression and DAB2IP knockdown on the proliferation and metastasis of MG-63 cells in Figure 2 and Figure 6 are also no longer repeatable. Subsequent analysis showed that the MG-63 cells used in this study were contaminated with HeLa cells, identified by short tandem repeat analysis. The authors believe cell contamination may be the main reason why the reported results are not reproducible. The authors no longer have confidence in the reliability of the results and would like to apologize for any inconvenience caused. The Editor-in-Chief agreed to retract the article.
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Affiliation(s)
- Wei Cai
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Haitao Jiang
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Yifan Yu
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Yong Xu
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Wenshan Zuo
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Shouguo Wang
- Orthopedics Department, Huai'an, Jiangsu Province 223300, China
| | - Zhen Su
- Anesthesiology Department, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province 223300, China.
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19
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Xiao G, Gao X, Sun X, Yang C, Zhang B, Sun R, Huang G, Li X, Liu J, Du N, Liu D, Liang R, Ren H, Qin S. miR-367 promotes tumor growth by inhibiting FBXW7 in NSCLC. Oncol Rep 2017; 38:1190-1198. [PMID: 28656290 DOI: 10.3892/or.2017.5755] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 06/12/2017] [Indexed: 11/06/2022] Open
Abstract
miR-367 is one of the most abundant miRNAs in human embryonic stem cells (hESCs) and is mainly involved in maintaining the pluripotency of stem cells. However, its role in cancer development remains poorly understood. In the present study, we explored the function and mechanism of the endogenous miR-367 in non-small cell lung cancer (NSCLC). In the present study, we demonstrated that the level of miR-367 in NSCLC was significantly higher than that in adjacent normal tissues, and its upregulation was positively correlated with tumor size, tumor differentiation and tumor-node-metastasis (TNM) stage. miR-367 was an indicator of a poorer prognosis in NSCLC patients. Furthermore, overexpression of miR-367 significantly inhibited apoptosis and enhanced proliferation by promoting cell cycle transition from G1 to S phase. In contrast, knockdown of miR-367 markedly reversed the cellular events observed with miR-367 overexpression. Moreover, we identified that F-box and WD repeat domain-containing 7 (FBXW7) is a novel target of miR-367. It reverses the oncogenic effects of miR-367 by downregulating its substrates, c-Myc and c-Jun, in NSCLC cells. Finally, studies in vivo revealed that knockdown of miR-367 inhibited the growth of xenografts in the nude mice by increasing the expression of FBXW7. In summary, our findings indicate that miR-367 exerts tumor-promoting effect by negatively regulating FBXW7 in NSCLC, and it could become a potential therapeutic target for NSCLC intervention.
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Affiliation(s)
- Guodong Xiao
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Xiao Gao
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Xin Sun
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Chengcheng Yang
- Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Boxiang Zhang
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Ruiying Sun
- Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Guanghong Huang
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Xiang Li
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Jian Liu
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Ning Du
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Dapeng Liu
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Rui Liang
- Department of Hepatobiliary Chest Surgery, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Force, Taiyuan, Shanxi, P.R. China
| | - Hong Ren
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
| | - Sida Qin
- Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
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20
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Zheng LQ, Chi SM, Li CX. Rab23's genetic structure, function and related diseases: a review. Biosci Rep 2017; 37:BSR20160410. [PMID: 28104793 PMCID: PMC5333778 DOI: 10.1042/bsr20160410] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 12/15/2016] [Accepted: 01/18/2017] [Indexed: 12/31/2022] Open
Abstract
Rab23 has been proven to play a role in membrane trafficking and protein transport in eukaryotic cells. Rab23 is also a negative regulator of the Sonic hedgehog (Shh) signaling pathway in an indirect way. The nonsense mutation and loss of protein of Rab23 has been associated with neural tube defect in mice and aberrant expression in various diseases in human such as neural system, breast, visceral, and cutaneous tumor. In addition, Rab23 may play joint roles in autophagosome formation during anti-infection process against Group A streptococcus. In this review, we give a brief review on the functions of Rab23, summarize the involvement of Rab23 in genetic research, membrane trafficking, and potential autophagy pathway, especially focus on tumor promotion, disease pathogenesis, and discuss the possible underlying mechanisms that are regulated by Rab23.
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Affiliation(s)
- Li-Qiang Zheng
- Department of Dermatology, Chinese PLA General Hospital, Beijing, China
- Department of Dermatology, the 251st Hospital of Chinese PLA, No.13.Jian'guo Road, Zhangjiakou City, Hebei Province, 075100, China
| | - Su-Min Chi
- Department of Physiology, Fourth Military Medical University, Xi'an, China
| | - Cheng-Xin Li
- Department of Dermatology, Chinese PLA General Hospital, Beijing, China
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21
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Qin X, Wang J, Wang X, Liu F, Jiang B, Zhang Y. Targeting Rabs as a novel therapeutic strategy for cancer therapy. Drug Discov Today 2017; 22:1139-1147. [PMID: 28390930 DOI: 10.1016/j.drudis.2017.03.012] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Revised: 02/18/2017] [Accepted: 03/21/2017] [Indexed: 12/13/2022]
Abstract
Rab GTPases constitute the largest family of small GTPases. Rabs regulate not only membrane trafficking but also cell signaling, growth and survival, and development. Increasingly, Rabs and their effectors are shown to be overexpressed or subject to loss-of-function mutations in a variety of disease settings, including cancer progression. This review provides an overview of dysregulated Rab proteins in cancer, and highlights the signaling and secretory pathways in which they operate, with the aim of identifying potential avenues for therapeutic intervention. Recent progress and perspectives for direct and/or indirect targeting of Rabs are also summarized.
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Affiliation(s)
- Xiaoyu Qin
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China
| | - Jiongyi Wang
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China
| | - Xinxin Wang
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China
| | - Feng Liu
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China
| | - Bin Jiang
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China.
| | - Yanjie Zhang
- Oncology Department, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China.
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22
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Palmini G, Marini F, Brandi ML. What Is New in the miRNA World Regarding Osteosarcoma and Chondrosarcoma? Molecules 2017; 22:E417. [PMID: 28272374 PMCID: PMC6155266 DOI: 10.3390/molecules22030417] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 03/03/2017] [Indexed: 02/06/2023] Open
Abstract
Despite the availability of multimodal and aggressive therapies, currently patients with skeletal sarcomas, including osteosarcoma and chondrosarcoma, often have a poor prognosis. In recent decades, advances in sequencing technology have revealed the presence of RNAs without coding potential known as non-coding RNAs (ncRNAs), which provides evidence that protein-coding genes account for only a small percentage of the entire genome. This has suggested the influence of ncRNAs during development, apoptosis and cell proliferation. The discovery of microRNAs (miRNAs) in 1993 underscored the importance of these molecules in pathological diseases such as cancer. Increasing interest in this field has allowed researchers to study the role of miRNAs in cancer progression. Regarding skeletal sarcomas, the research surrounding which miRNAs are involved in the tumourigenesis of osteosarcoma and chondrosarcoma has rapidly gained traction, including the identification of which miRNAs act as tumour suppressors and which act as oncogenes. In this review, we will summarize what is new regarding the roles of miRNAs in chondrosarcoma as well as the latest discoveries of identified miRNAs in osteosarcoma.
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Affiliation(s)
- Gaia Palmini
- Department of Surgery and Translational Medicine, University of Florence, Florence 50134, Italy.
| | - Francesca Marini
- Department of Surgery and Translational Medicine, University of Florence, Florence 50134, Italy.
| | - Maria Luisa Brandi
- Department of Surgery and Translational Medicine, University of Florence, Florence 50134, Italy.
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23
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Liu HT, Wang YW, Xing AY, Shi DB, Zhang H, Guo XY, Xu J, Gao P. Prognostic Value of microRNA Signature in Patients with Gastric Cancers. Sci Rep 2017; 7:42806. [PMID: 28202938 PMCID: PMC5311868 DOI: 10.1038/srep42806] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Accepted: 01/13/2017] [Indexed: 01/28/2023] Open
Abstract
The occurrence of lymph node metastases (LNM) after endoscopic submucosal dissection (ESD) in patients with gastric cancer (GC) leads to poor prognosis. However, few biomarkers are available to predict LNM in GC patients. Thus, we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC samples that were randomized into a training set and a testing set (each, 51 cases). Using logistic regression, we identified 4-miRNA (miR-27b, miR-128, miR-100 and miR-214) signatures for predicting LNM in GC patients. Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores. Meanwhile, the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients. In addition, Cox regression analysis indicated that a 2-miRNA signature (miR-27b and miR-214) or a miR-214/N stage signature was predictive of survival for GC patients. This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients’ survival.
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Affiliation(s)
- Hai-Ting Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Ya-Wen Wang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Ai-Yan Xing
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Duan-Bo Shi
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Hui- Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Xiang-Yu Guo
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
| | - Jing- Xu
- Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China.,Department of Pathology, Qingdao Central Hospital, Qingdao, P.R. China
| | - Peng Gao
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, School of Medicine, Shandong University, Jinan, P.R. China
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24
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Chen W, Guo S, Wang S. MicroRNA-16 Alleviates Inflammatory Pain by Targeting Ras-Related Protein 23 (RAB23) and Inhibiting p38 MAPK Activation. Med Sci Monit 2016; 22:3894-3901. [PMID: 27770129 PMCID: PMC5081236 DOI: 10.12659/msm.897580] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. Material/Methods Inflammatory pain was induced by injection of complete Freund’s adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4–L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR). In addition, luciferase reporter assay was performed to explore whether RAB23 was a target of miR-16, and qRT-PCR and Western blotting were used to confirm the regulation between RAB23 and miR-16. Results The level of miR-16 was significantly decreased in the CFA-induced inflammatory pain. Intrathecal injection of miR-16 alleviates pain response and raised pain threshold. The level of RAB23 was significantly increased in the pain model, and intrathecal injection of RAB23 aggravated pain response. Luciferase reporter assay confirmed that RAB23 was a direct target of miR-16, and RAB23 was negatively regulated by miR-16. In addition, we found that simultaneous administration of SB203580 and miR-16 further alleviates pain response compared to only administration of miR-16. Conclusions Our findings suggest that miR-16 relieves chronic inflammatory pain by targeting RAB23 and inhibiting p38 MAPK activation.
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Affiliation(s)
- Wenjin Chen
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Shengdong Guo
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong, China (mainland)
| | - Shenggang Wang
- Department of Anesthesiology, Linyi People's Hospital, Linyi, Shandong, China (mainland)
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Liu HT, Xing AY, Chen X, Ma RR, Wang YW, Shi DB, Zhang H, Li P, Chen HF, Li YH, Gao P. MicroRNA-27b, microRNA-101 and microRNA-128 inhibit angiogenesis by down-regulating vascular endothelial growth factor C expression in gastric cancers. Oncotarget 2016; 6:37458-70. [PMID: 26460960 PMCID: PMC4741941 DOI: 10.18632/oncotarget.6059] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Accepted: 09/23/2015] [Indexed: 01/30/2023] Open
Abstract
Vascular Endothelial Growth Factor C (VEGF-C) has critical roles in angiogenesis in human cancers; however, the underlying mechanisms regulating VEGF-C expression remain largely unknown. In the present study, VEGF-C protein expression and the density of blood vessels or lymphatic vessels were determined by immunohistochemistry in 103 cases of gastric cancer tissues. Suppression of VEGF-C by miR-27b, miR-101 and miR-128 was investigated by luciferase assays, Western blot and ELISA. The miRNAs expression levels were detected in human gastric cancers by real-time quantitative PCR. Cell proliferation, migration and invasion assays were performed to assess the effect of miRNAs on gastric cancer cells and human umbilical vascular endothelial cells (HUVECs). Our data showed that high VEGF-C expression was significantly associated with increased tumor size, advanced TNM classification and clinical stage, higher microvessel density (MVD) and lymphatic density (LVD), as well as poor survival in patients with gastric cancer. Furthermore, VEGF-C was found to be a direct target gene of miR-27b, miR-101, and miR-128. The expression levels of the three miRNAs were inversely correlated with MVD. Overexpression of miR-27b, miR-101, or miR-128 suppressed migration, proliferation activity, and tube formation in HUVECs by repressing VEGF-C secretion in gastric cancer cells. We conclude that miR-27b, miR-101 and miR-128 inhibit angiogenesis by down-regulating VEGF-C expression in gastric cancers.
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Affiliation(s)
- Hai-Ting Liu
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Ai-Yan Xing
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Xu Chen
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Ran-Ran Ma
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Ya-Wen Wang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Duan-Bo Shi
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Hui Zhang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Peng Li
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
| | - Hong-Fang Chen
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, Qingzhou Center Hospital, Weifang, P.R. China
| | - Yu-Hong Li
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China.,Department of Pathology, Liaocheng Peoples Hospital, Liaocheng, P.R. China
| | - Peng Gao
- Department of Pathology, Qilu Hospital, Shandong University, Jinan, P.R. China
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26
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Rab23 activities and human cancer—emerging connections and mechanisms. Tumour Biol 2016; 37:12959-12967. [DOI: 10.1007/s13277-016-5207-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 07/13/2016] [Indexed: 12/19/2022] Open
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Xu J, Lin H, Li G, Sun Y, Chen J, Shi L, Cai X, Chang C. The miR-367-3p Increases Sorafenib Chemotherapy Efficacy to Suppress Hepatocellular Carcinoma Metastasis through Altering the Androgen Receptor Signals. EBioMedicine 2016; 12:55-67. [PMID: 27688096 PMCID: PMC5078576 DOI: 10.1016/j.ebiom.2016.07.013] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 06/30/2016] [Accepted: 07/12/2016] [Indexed: 01/08/2023] Open
Abstract
The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3′UTR of MDM2 to decrease MDM2 protein expression. The resultant increase of AR expression might then promote the expression of FKBP5 and PHLPP, thus dephosphorylating and inactivating AKT and ERK, to suppress the HCC cell invasion. Interestingly, the suppression of pAKT by miR-367-3p could subsequently attenuate the phosphorylation of AR and MDM2, giving rise to additional enhancement of AR protein expression, effectively forming a positive feedback loop. Together, these results suggest that miR-367-3p may function as an AR enhancer to increase Sorafenib chemotherapy efficacy via altering the MDM2/AR/FKBP5/PHLPP/(pAKT and pERK) signals to better suppress HCC metastasis. Successful development of this newly combined chemotherapy in the future may help us to better suppress the HCC metastasis at late stages.
As an HCC metastasis suppressor, miR-367-3p is expressed at lower levels and positively correlated with AR in advanced HCC. The miR-367-3p enhances Sorafenib chemotherapy efficacy via MDM2-AR-(pAKT and pERK) signals and a positive feedback loop. Successful clinical application of these findings in the future may help us to better retard HCC metastasis at late stages. MiRNAs may be promising candidates for therapeutic targets. In this study, we show that miR-367-3p could enhance Sorafenib chemotherapy efficacy via altering MDM2-AR-(pAKT and pERK) signals and formed a positive feedback loop to better suppress the metastasis of hepatocellular carcinoma. Successful clinical application of these findings in the future may help us to better suppress the process of late-stage hepatocellular carcinoma.
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Affiliation(s)
- Junjie Xu
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China; George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Hui Lin
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
| | - Gonghui Li
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
| | - Yin Sun
- George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Jiang Chen
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
| | - Liang Shi
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China; George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Xiujun Cai
- Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
| | - Chawnshang Chang
- George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA; Sex Hormone Research Center, China Medical University/Hospital, Taichung 404, Taiwan.
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MiR-367 negatively regulates apoptosis induced by adriamycin in osteosarcoma cells by targeting KLF4. J Bone Oncol 2016; 5:51-6. [PMID: 27335771 PMCID: PMC4908187 DOI: 10.1016/j.jbo.2016.02.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 02/09/2016] [Indexed: 12/16/2022] Open
Abstract
Diverse functions of microRNAs have been investigated in tumorigenesis in osteosarcoma (OS), involving the regulation of proliferation, invasion, migration, apoptosis and drug resistance. MiR-367 was found to be an oncogene and increased in OS. However, the function of miR-367 in drug resistance in OS cells is still unknown. In this study, we found that miR-367 was up-regulated in OS tissues and OS cell cultures. Meanwhile, treatment with adriamycin (ADR) induced apoptosis of OS cells with upregulation of miR-367. Notably, KLF4 was demonstrated to be a direct target of miR-367 by gene reporter assay, and miR-367 significantly blocked both mRNA and protein level of KLF4. In addition, overexpression of miR-367 markedly suppressed the increase of KLF4 induced by ADR in OS cells, as well as Bax and cleaved caspase-3, which were significantly reversed by anti-miR-367 transfection. Taken together, our data demonstrates that miR-367 and KLF4 play important roles in OS treatment and ADR resistance, suggesting that miR-367 is a potential biomarker of chemotherapy resistance in OS and also probably a novel therapeutic target against OS.
miR-367 functions as an oncogene in OS targeting the tumor suppressor KLF4. ADR induces apoptosis in OS via miR-367/KLF4/Bax signaling pathway. miR-367 enhances the resistance of ADR to OS cells through suppressing KLF4. miR-367 could be a potential biomarker of chemotherapy resistance against OS.
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29
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Wu X, Tang H, Liu G, Wang H, Shu J, Sun F. miR-448 suppressed gastric cancer proliferation and invasion by regulating ADAM10. Tumour Biol 2016; 37:10545-51. [PMID: 26852749 DOI: 10.1007/s13277-016-4942-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 01/29/2016] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRNAs) are a class of short, noncoding RNAs that act a crucial role in tumor development. Previous studies showed that miR-448 expression was deregulated in many tumors. However, the role of miR-448 in gastric cancer (GC) remains unknown. In our study, we demonstrated that miR-448 expression was downregulated in GC tissues compared with the corresponding nontumor tissues. We also showed that miR-448 expression was downregulated in GC cell lines. Ectopic expression of miR-448 suppressed GC cell proliferation, colony formation, and invasion. Moreover, we identified A Disintegrin And Metalloproteinases 10 (ADAM10) as a direct target gene of miR-448 in GC cell. ADAM10 expression was upregulated in GC tissues and cells. Furthermore, the expression level of miR-448 was negatively correlated with the expression level of ADAM10 in GC tissues. Moreover, ADAM10 overexpression rescued the effect of miR-448-mediated GC cell proliferation, colony formation, and invasion. These results demonstrated that miR-448 might play as a tumor suppressor miRNA partly through targeting ADAM10 expression.
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Affiliation(s)
- Xuesong Wu
- Department of Gastrointenstinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China
| | - Haoran Tang
- Department of Gastrointenstinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China
| | - Guobin Liu
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China
| | - Hui Wang
- Department of Gastroenterology, The Affiliated YanAn Hospital of Kunming Medical University, Kunming, 650051, Yunnan, China
| | - Jie Shu
- Department of Gastrointenstinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China
| | - Feng Sun
- Department of Gastrointenstinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China.
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30
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Zhao Y, Lu G, Ke X, Lu X, Wang X, Li H, Ren M, He S. miR-488 acts as a tumor suppressor gene in gastric cancer. Tumour Biol 2016. [PMID: 26738864 DOI: 10.1007/s13277-015-4645-y.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that modulate development, cell proliferation, and apoptosis. The deregulated expression of microRNAs is found in carcinogenesis including gastric cancer (GC). In this study, we showed that the expression levels of miR-488 were downregulated in GC tissues compared to in non-tumor tissues. In addition, the expression of miR-488 was also lower in GC cell lines in contrast with the gastric epithelial cell line (GES). In addition, the expression level of miR-488 was negatively correlated with the TNM stage in GC patients, and lower miR-488 expression was found in tumors with advanced TNM stage. The ectopic expression of miR-488 suppressed the GC cell proliferation, cell cycle, colony information, and migration. PAX6 was identified as a direct target gene of miR-488 in HGC-27. Moreover, we found that the expression level of PAX6 was upregulated in the GC tissues compared with the non-tumor tissues. The PAX6 expression level was correlated with the cancer TNM stage, and higher PAX6 expression was found in tumors with advanced TNM stage. Furthermore, there was an inverse correlation between PAX6 and miR-488 expression levels in GC tissues. Therefore, these studies demonstrated that miR-488 might act as a tumor suppressor miRNA in the development of GC.
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Affiliation(s)
- Yan Zhao
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Guifang Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xiquan Ke
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xinlan Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xin Wang
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Hongxia Li
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Mudan Ren
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
| | - Shuixiang He
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
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Meng X, Lu P, Fan Q. miR-367 promotes proliferation and invasion of hepatocellular carcinoma cells by negatively regulating PTEN. Biochem Biophys Res Commun 2016; 470:187-191. [PMID: 26772880 DOI: 10.1016/j.bbrc.2016.01.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 01/05/2016] [Indexed: 01/26/2023]
Abstract
MicroRNAs play important roles in the carcinogenesis of many types of cancers by inhibiting gene expression at posttranscriptional level. However, the roles of microRNAs in hepatocellular carcinoma, are still unclear. Here, we identified that miR-367 promotes hepatocellular carcinoma (HCC) cell proliferation by negatively regulates its target gene PTEN. The expression of miR-367 and PTEN are significantly inverse correlated in 35 HCC patients. In HCC cell line, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-367, while miR-367 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-367 mimics significantly promoted the migration and invasion of HCC cells, whereas miR-367 inhibitors significantly reduced cell migration and invasion. Luciferase assays confirmed that miR-367 directly bound to the 3'untranslated region of PTEN, and western blotting showed that miR-367 suppressed the expression of PTEN at the protein levels. This study indicated that miR-367 negatively regulates PTEN and promotes proliferation and invasion of HCC cells. Thus, miR-367 may represent a potential therapeutic target for HCC intervention.
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Affiliation(s)
- Xiangrui Meng
- Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Peng Lu
- Gastrointestinal Surgery Department, People's Hospital of Zhengzhou, Zhengzhou, China
| | - Qingxia Fan
- Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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32
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Zhao Y, Lu G, Ke X, Lu X, Wang X, Li H, Ren M, He S. miR-488 acts as a tumor suppressor gene in gastric cancer. Tumour Biol 2016; 37:8691-8. [PMID: 26738864 DOI: 10.1007/s13277-015-4645-y] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Accepted: 12/13/2015] [Indexed: 12/12/2022] Open
Affiliation(s)
- Yan Zhao
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Guifang Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xiquan Ke
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xinlan Lu
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xin Wang
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Hongxia Li
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Mudan Ren
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
| | - Shuixiang He
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
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Yang Q, Zhang RW, Sui PC, He HT, Ding L. Dysregulation of non-coding RNAs in gastric cancer. World J Gastroenterol 2015; 21:10956-10981. [PMID: 26494954 PMCID: PMC4607897 DOI: 10.3748/wjg.v21.i39.10956] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/28/2015] [Accepted: 09/15/2015] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is one of the most common cancers in the world and a significant threat to the health of patients, especially those from China and Japan. The prognosis for patients with late stage GC receiving the standard of care treatment, including surgery, chemotherapy and radiotherapy, remains poor. Developing novel treatment strategies, identifying new molecules for targeted therapy, and devising screening techniques to detect this cancer in its early stages are needed for GC patients. The discovery of non-coding RNAs (ncRNAs), primarily microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), helped to elucidate the mechanisms of tumorigenesis, diagnosis and treatment of GC. Recently, significant research has been conducted on non-coding RNAs and how the regulatory dysfunction of these RNAs impacts the tumorigenesis of GC. In this study, we review papers published in the last five years concerning the dysregulation of non-coding RNAs, especially miRNAs and lncRNAs, in GC. We summarize instances of aberrant expression of the ncRNAs in GC and their effect on survival-related events, including cell cycle regulation, AKT signaling, apoptosis and drug resistance. Additionally, we evaluate how ncRNA dysregulation affects the metastatic process, including the epithelial-mesenchymal transition, stem cells, transcription factor activity, and oncogene and tumor suppressor expression. Lastly, we determine how ncRNAs affect angiogenesis in the microenvironment of GC. We further discuss the use of ncRNAs as potential biomarkers for use in clinical screening, early diagnosis and prognosis of GC. At present, no ideal ncRNAs have been identified as targets for the treatment of GC.
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Kaid C, Silva PBG, Cortez BA, Rodini CO, Semedo-Kuriki P, Okamoto OK. miR-367 promotes proliferation and stem-like traits in medulloblastoma cells. Cancer Sci 2015; 106:1188-95. [PMID: 26250335 PMCID: PMC4582988 DOI: 10.1111/cas.12733] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Revised: 06/10/2015] [Accepted: 06/30/2015] [Indexed: 01/03/2023] Open
Abstract
In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells. Basal expression of primary and mature forms of miR-367 were detected in four human medulloblastoma cell lines and expression of the latter was found to be upregulated upon enforced expression of OCT4A. Transient overexpression of miR-367 significantly enhanced tumor features typically correlated with poor prognosis; namely, cell proliferation, 3-D tumor spheroid cell invasion and the ability to generate neurosphere-like structures enriched in CD133 expressing cells. A concurrent downregulation of the miR-367 cancer-related targets RYR3, ITGAV and RAB23, was also detected in miR-367-overexpressing cells. Overall, these findings support the pro-oncogenic activity of miR-367 in medulloblastoma and reveal a possible mechanism contributing to tumor aggressiveness, which could be further explored to improve patient stratification and treatment of this important type of pediatric brain cancer.
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Affiliation(s)
- Carolini Kaid
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
| | - Patrícia B G Silva
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
| | - Beatriz A Cortez
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
| | - Carolina O Rodini
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
| | - Patricia Semedo-Kuriki
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
| | - Oswaldo K Okamoto
- Department of Genetics and Evolutionary Biology, Human Genome and Stem Cell Research Center, Biosciences Institute, University of São Paulo, 05508-090 São Paulo, SP, Brazil
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