Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y, Li Q, Qiao T, Zhao Q, Nie Y, Fan D. MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet 2010;6:e1000879. [PMID: 20300657 PMCID: PMC2837402 DOI: 10.1371/journal.pgen.1000879] [Citation(s) in RCA: 361] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2009] [Accepted: 02/10/2010] [Indexed: 12/11/2022] Open

For:	Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y, Li Q, Qiao T, Zhao Q, Nie Y, Fan D. MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet 2010;6:e1000879. [PMID: 20300657 PMCID: PMC2837402 DOI: 10.1371/journal.pgen.1000879] [Citation(s) in RCA: 361] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2009] [Accepted: 02/10/2010] [Indexed: 12/11/2022] Open

Number

Cited by Other Article(s)

Zhang J, Zhong S, Lai S, Zhang Y, Chen G, Huang D, Yan S, Chen P, Lu X, Yin J, Chen C, Wang Y, Jia Y. MIR218 polygenic risk score is associated with cognitive function and neurochemical metabolites among patients with depressed bipolar disorders. J Affect Disord 2025;371:104-112. [PMID: 39561923 DOI: 10.1016/j.jad.2024.11.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/22/2024] [Accepted: 11/13/2024] [Indexed: 11/21/2024]

Wang J, Xu J, Liu X, Tong Y, Xu Z. Establishment of highly metastatic sublines and insights into telomerase expression during tumor metastasis using a microfluidic system. Talanta 2024;280:126690. [PMID: 39126963 DOI: 10.1016/j.talanta.2024.126690] [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: 06/24/2024] [Revised: 08/04/2024] [Accepted: 08/06/2024] [Indexed: 08/12/2024]

Abstract

Metastasis is an important hallmark of malignant tumors, and telomerase often exhibits high expression in these tumors. Monitoring the real-time dynamics of telomerase will provide valuable insights into its association with tumor metastasis. In this study, we described a microfluidic system for screening highly metastatic sublines based on differential cell invasiveness, investigated telomerase expression in the process of tumor metastasis and explored the genes and signaling pathways involved in tumor metastasis. Cells with different metastasis abilities were efficiently classified into different channels, and the fluorescence imaging visually demonstrates that cells with higher metastasis ability have stronger telomerase activity. In addition, we successfully established the high-metastasis-ability LoVo subline (named as LoVo-H) and low-metastasis-ability LoVo subline (named as LoVo-L) from the human colorectal cancer LoVo cell lines through only one round of selection using the system. The results show that the LoVo-H cells display superior proliferation and invasiveness compared to LoVo-L cells. Furthermore, 6776 differentially expressed genes of LoVo-H compared with LoVo-L were identified by transcriptome sequencing. The genes associated with telomerase activity, cell migration and the epithelial to mesenchymal transition were up-regulated in LoVo-H, and PI3K-Akt signaling pathway, extracellular matrix-receptor interaction and Rap1 signaling pathway were significantly enriched in LoVo-H. This microfluidic system is a highly effective tool for selecting highly metastatic sublines and the LoVo-H subline established through this system presents a promising model for tumor metastasis research. Furthermore, this work preliminarily reveals telomerase expression during tumor metastasis and provides a new strategy for studying tumor metastasis and cancer diagnosis.

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Joudaki N, Khodadadi A, Shamshiri M, Dehnavi S, Asadirad A. Alterations in the expression of serum-derived exosome-enclosed inflammatory microRNAs in Covid-19 patients. Heliyon 2024;10:e39303. [PMID: 39640730 PMCID: PMC11620257 DOI: 10.1016/j.heliyon.2024.e39303] [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: 06/11/2024] [Revised: 10/05/2024] [Accepted: 10/11/2024] [Indexed: 12/07/2024] Open

Liang Y, Li J, Li T, Li M, Liao H, Liu Y, Yao Y, Yang L, Lei X. Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway. Carcinogenesis 2024;45:773-785. [PMID: 38829328 DOI: 10.1093/carcin/bgae036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 05/18/2024] [Accepted: 06/01/2024] [Indexed: 06/05/2024] Open

Affiliation(s)

Yahang Liang Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Junyu Li Department of Orthopedics, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
Tao Li Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Mingming Li Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Hualin Liao Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Yang Liu Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Yao Yao Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China
Lingling Yang Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
Xiong Lei Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China Gastrointestinal Surgical Institute, Nanchang University, Nanchang 330006, Jiangxi, China

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Markouli M, Papachristou A, Politis A, Boviatsis E, Piperi C. Emerging Role of the Slit/Roundabout (Robo) Signaling Pathway in Glioma Pathogenesis and Potential Therapeutic Options. Biomolecules 2024;14:1231. [PMID: 39456164 PMCID: PMC11506736 DOI: 10.3390/biom14101231] [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: 07/31/2024] [Revised: 09/20/2024] [Accepted: 09/27/2024] [Indexed: 10/28/2024] Open

He H, Hao D, Tian L, Zhu C, Guo L, Zhang K, Zhu S. Research on the expression of Mir-218-2 in the serum of patients with papillary thyroid cancer and its clinical significance. Eur J Transl Myol 2024;34:12678. [PMID: 39221591 PMCID: PMC11487670 DOI: 10.4081/ejtm.2024.12678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 06/17/2024] [Indexed: 09/04/2024] Open

Li F, Yu H, Qi A, Zhang T, Huo Y, Tu Q, Qi C, Wu H, Wang X, Zhou J, Hu L, Ouyang H, Pang D, Xie Z. Regulatory Non-Coding RNAs during Porcine Viral Infections: Potential Targets for Antiviral Therapy. Viruses 2024;16:118. [PMID: 38257818 PMCID: PMC10818342 DOI: 10.3390/v16010118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/07/2024] [Accepted: 01/10/2024] [Indexed: 01/24/2024] Open

Affiliation(s)

Feng Li Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Hao Yu Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Aosi Qi Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Tianyi Zhang Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Yuran Huo Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Qiuse Tu Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Chunyun Qi Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Heyong Wu Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Xi Wang Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Jian Zhou Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Lanxin Hu Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.)
Hongsheng Ouyang Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.) Chongqing Research Institute, Jilin University, Chongqing 401120, China Chongqing Jitang Biotechnology Research Institute Co., Ltd., Chongqing 401120, China
Daxin Pang Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.) Chongqing Research Institute, Jilin University, Chongqing 401120, China Chongqing Jitang Biotechnology Research Institute Co., Ltd., Chongqing 401120, China
Zicong Xie Key Laboratory of Zoonosis Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China; (F.L.); (H.Y.); (A.Q.); (T.Z.); (Y.H.); (Q.T.); (C.Q.); (H.W.); (X.W.); (J.Z.); (L.H.); (H.O.) Chongqing Research Institute, Jilin University, Chongqing 401120, China Chongqing Jitang Biotechnology Research Institute Co., Ltd., Chongqing 401120, China

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Lyu Y, Xie F, Chen B, Shin WS, Chen W, He Y, Leung KT, Tse GMK, Yu J, To KF, Kang W. The nerve cells in gastrointestinal cancers: from molecular mechanisms to clinical intervention. Oncogene 2024;43:77-91. [PMID: 38081962 PMCID: PMC10774121 DOI: 10.1038/s41388-023-02909-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: 10/11/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 01/10/2024]

Affiliation(s)

Yang Lyu Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China CUHK-Shenzhen Research Institute, Shenzhen, China
Fuda Xie Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China CUHK-Shenzhen Research Institute, Shenzhen, China
Bonan Chen Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China CUHK-Shenzhen Research Institute, Shenzhen, China
Wing Sum Shin Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Wei Chen Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
Yulong He Guangdong Provincial Key Laboratory of Digestive Cancer Research, Digestive Diseases Center, Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
Kam Tong Leung Department of Pediatrics, The Chinese University of Hong Kong, Hong Kong, China
Gary M K Tse Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Jun Yu Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
Ka Fai To Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
Wei Kang Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Sir Y.K. Pao Cancer Center, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China. CUHK-Shenzhen Research Institute, Shenzhen, China.

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Shojaei S, Moradi-Chaleshtori M, Paryan M, Koochaki A, Sharifi K, Mohammadi-Yeganeh S. Mesenchymal stem cell-derived exosomes enriched with miR-218 reduce the epithelial-mesenchymal transition and angiogenesis in triple-negative breast cancer cells. Eur J Med Res 2023;28:516. [PMID: 37968694 PMCID: PMC10647065 DOI: 10.1186/s40001-023-01463-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 10/19/2023] [Indexed: 11/17/2023] Open

Baran O, Karaoglu AC, Kara E, Budun O, Katar S, Yilmaz SG, Akdeniz FT, Ambarcioglu MA, Demirel N, Turk O, Ozdemir NG, Yaltirik CK, Isbir T. Expression of miRNA-451 and miRNA-885 in Meningiomas. In Vivo 2023;37:2473-2479. [PMID: 37905647 PMCID: PMC10621404 DOI: 10.21873/invivo.13354] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/30/2023] [Accepted: 08/31/2023] [Indexed: 11/02/2023]

Taylor SR, Kobayashi M, Vilella A, Tiwari D, Zolboot N, Du JX, Spencer KR, Hartzell A, Girgiss C, Abaci YT, Shao Y, De Sanctis C, Bellenchi GC, Darnell RB, Gross C, Zoli M, Berg DK, Lippi G. MicroRNA-218 instructs proper assembly of hippocampal networks. eLife 2023;12:e82729. [PMID: 37862092 PMCID: PMC10637775 DOI: 10.7554/elife.82729] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 10/10/2023] [Indexed: 10/21/2023] Open

Affiliation(s)

Seth R Taylor Division of Biological Sciences, University of California, San DiegoLa JollaUnited States
Mariko Kobayashi Laboratory of Molecular Neuro-oncology, Howard Hughes Medical Institute, Rockefeller UniversityNew YorkUnited States
Antonietta Vilella Department of Biomedical, Metabolic and Neural Sciences; Center for Neuroscience and Neurotechnology (CfNN), University of Modena and Reggio EmiliaModenaItaly
Durgesh Tiwari Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of MedicineCincinnatiUnited States Department of Pediatrics, University of Cincinnati College of MedicineCincinnatiUnited States
Norjin Zolboot Department of Neuroscience, Scripps Research InstituteLa JollaUnited States
Jessica X Du Department of Neuroscience, Scripps Research InstituteLa JollaUnited States
Kathryn R Spencer Department of Neuroscience, Scripps Research InstituteLa JollaUnited States
Andrea Hartzell Department of Neuroscience, Scripps Research InstituteLa JollaUnited States
Carol Girgiss Division of Biological Sciences, University of California, San DiegoLa JollaUnited States
Yusuf T Abaci Division of Biological Sciences, University of California, San DiegoLa JollaUnited States
Yufeng Shao Department of Neuroscience, Scripps Research InstituteLa JollaUnited States
Claudia De Sanctis Institute of Genetics and Biophysics A Buzzati-TraversoNaplesItaly
Gian Carlo Bellenchi Institute of Genetics and Biophysics A Buzzati-TraversoNaplesItaly IRCCS Fondazione Santa LuciaRomeItaly
Robert B Darnell Laboratory of Molecular Neuro-oncology, Howard Hughes Medical Institute, Rockefeller UniversityNew YorkUnited States
Christina Gross Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of MedicineCincinnatiUnited States Department of Pediatrics, University of Cincinnati College of MedicineCincinnatiUnited States
Michele Zoli Department of Biomedical, Metabolic and Neural Sciences; Center for Neuroscience and Neurotechnology (CfNN), University of Modena and Reggio EmiliaModenaItaly
Darwin K Berg Division of Biological Sciences, University of California, San DiegoLa JollaUnited States
Giordano Lippi Department of Neuroscience, Scripps Research InstituteLa JollaUnited States

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Kim EY, Kim JE, Chung SH, Park JE, Yoon D, Min HJ, Sung Y, Lee SB, Kim SW, Chang EJ. Concomitant induction of SLIT3 and microRNA-218-2 in macrophages by toll-like receptor 4 activation limits osteoclast commitment. Cell Commun Signal 2023;21:213. [PMID: 37596575 PMCID: PMC10436635 DOI: 10.1186/s12964-023-01226-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 07/12/2023] [Indexed: 08/20/2023] Open

Abstract

BACKGROUND

Toll-like receptor 4 (TLR4) conducts a highly regulated inflammatory process by limiting the extent of inflammation to avoid toxicity and tissue damage, even in bone tissues. Thus, it is plausible that strategies for the maintenance of normal bone-immunity to prevent undesirable bone damage by TLR4 activation can exist, but direct evidence is still lacking.

METHODS

Osteoclast precursors (OCPs) obtained from WT or Slit3-deficient mice were differentiated into osteoclast (OC) with macrophage colony-stimulating factor (M-CSF), RANK ligand (RANKL) and lipopolysaccharide (LPS) by determining the number of TRAP-positive multinuclear cells (TRAP+ MNCs). To determine the alteration of OCPs population, fluorescence-activated cell sorting (FACS) was conducted in bone marrow cells in mice after LPS injection. The severity of bone loss in LPS injected WT or Slit3-deficient mice was evaluated by micro-CT analysis.

RESULT

We demonstrate that TLR4 activation by LPS inhibits OC commitment by inducing the concomitant expression of miR-218-2-3p and its host gene, Slit3, in mouse OCPs. TLR4 activation by LPS induced SLIT3 and its receptor ROBO1 in BMMs, and this SLIT3-ROBO1 axis hinders RANKL-induced OC differentiation by switching the protein levels of C/EBP-β isoforms. A deficiency of SLIT3 resulted in increased RANKL-induced OC differentiation, and the elevated expression of OC marker genes including Pu.1, Nfatc1, and Ctsk. Notably, Slit3-deficient mice showed expanded OCP populations in the bone marrow. We also found that miR-218-2 was concomitantly induced with SLIT3 expression after LPS treatment, and that this miRNA directly suppressed Tnfrsf11a (RANK) expression at both gene and protein levels, linking it to a decrease in OC differentiation. An endogenous miR-218-2 block rescued the expression of RANK and subsequent OC formation in LPS-stimulated OCPs. Aligned with these results, SLIT3-deficient mice displayed increased OC formation and reduced bone density after LPS challenge.

CONCLUSION

Our findings suggest that the TLR4-dependent concomitant induction of Slit3 and miR-218-2 targets RANK in OCPs to restrain OC commitment, thereby avoiding an uncoordinated loss of bone through inflammatory processes. These observations provide a mechanistic explanation for the role of TLR4 in controlling the commitment phase of OC differentiation. Video Abstract.

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Affiliation(s)

Eun-Young Kim Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Ji-Eun Kim Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Soo-Hyun Chung Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Ji-Eun Park Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea
Dohee Yoon Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Hyo-Jin Min Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Yoolim Sung Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Soo Been Lee Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
Seong Who Kim Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea. Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
Eun-Ju Chang Department of Biochemistry and Molecular Biology, Asan Medical Center and AMIST, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea. Stem Cell Immunomodulation Research Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.

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Lu G, Du R, Dong J, Sun Y, Zhou F, Feng F, Feng B, Han Y, Shang Y. Cancer associated fibroblast derived SLIT2 drives gastric cancer cell metastasis by activating NEK9. Cell Death Dis 2023;14:421. [PMID: 37443302 PMCID: PMC10344862 DOI: 10.1038/s41419-023-05965-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 06/29/2023] [Accepted: 07/06/2023] [Indexed: 07/15/2023]

Abstract

The secretory properties of cancer-associated fibroblasts (CAFs) play predominant roles in shaping a pro-metastatic tumor microenvironment. The present study demonstrated that SLIT2, an axon guidance protein, produced by CAFs and promoted gastric cancer (GC) metastasis in two gastric cancer cell lines (AGS and MKN45) by binding to roundabout guidance receptor 1 (ROBO1). Mass-spectrometry analysis revealed that ROBO1 could interact with NEK9, a serine/threonine kinase. And their mutual binding activities were further enhanced by SLIT2. Domain analysis revealed the kinase domain of NEK9 was critical in its interaction with the intracellular domain (ICD) of ROBO1, and it also directly phosphorylated tripartite motif containing 28 (TRIM28) and cortactin (CTTN) in AGS and MKN45 cells. TRIM28 function as a transcriptional elongation factor, which directly facilitate CTTN activation. In addition, Bioinformatics analysis and experimental validation identified transcriptional regulation of STAT3 and NF-κB p100 by TRIM28, and a synergetic transcription of CTTN by STAT3 and NF-κB p100 was also observed in AGS and MKN45. Therefore, CAF-derived SLIT2 increased the expression and phosphorylation levels of CTTN, which induced cytoskeletal reorganization and GC cells metastasis. A simultaneous increase in the expression levels of NEK9, TRIM28 and CTTN was found in metastatic GC lesions compared with paired non-cancerous tissues and primary cancer lesions via IHC and Multiplex IHC. The analysis of the data from a cohort of patients with GC revealed that increased levels of NEK9, TRIM28 and CTTN were associated with a decreased overall survival rate. On the whole, these findings revealed the connections of CAFs and cancer cells through SLIT2/ROBO1 and inflammatory signaling, and the key molecules involved in this process may serve as potential biomarkers and therapeutic targets for GC.

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Hashemi M, Gholami S, Raesi R, Sarhangi S, Mahmoodieh B, Koohpar ZK, Goharrizi MASB, Behroozaghdam M, Entezari M, Salimimoghadam S, Zha W, Rashidi M, Abdi S, Taheriazam A, Nabavi N. Biological and therapeutic viewpoints towards role of miR-218 in human cancers: Revisiting molecular interactions and future clinical translations. Cell Signal 2023:110786. [PMID: 37380085 DOI: 10.1016/j.cellsig.2023.110786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/20/2023] [Accepted: 06/26/2023] [Indexed: 06/30/2023]

Affiliation(s)

Mehrdad Hashemi Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
Sadaf Gholami Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
Rasoul Raesi Department of Health Services Management, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical-Surgical Nursing, Mashhad University of Medical Sciences, Mashhad, Iran
Sareh Sarhangi Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
Behnaz Mahmoodieh Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Zeinab Khazaei Koohpar Department of Cell and Molecular Biology, Faculty of Biological Sciences,Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
Mohammad Ali Shekhi Beig Goharrizi Faculty of Biotechnology, University of Tehran, Tehran, Iran
Mitra Behroozaghdam Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
Maliheh Entezari Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
Shokooh Salimimoghadam Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Wenliang Zha Second Affiliated Hospital, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Mohsen Rashidi Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Soheila Abdi Department of Physics, Safadasht Branch, Islamic Azad university, Tehran, Iran.
Afshin Taheriazam Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Noushin Nabavi Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6 Vancouver, BC, Canada.

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Lucarini V, Nardozi D, Angiolini V, Benvenuto M, Focaccetti C, Carrano R, Besharat ZM, Bei R, Masuelli L. Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion. Biomedicines 2023;11:1761. [PMID: 37371856 DOI: 10.3390/biomedicines11061761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open

Kim K, Ryu TY, Jung E, Han TS, Lee J, Kim SK, Roh YN, Lee MS, Jung CR, Lim JH, Hamamoto R, Lee HW, Hur K, Son MY, Kim DS, Cho HS. Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis. Exp Mol Med 2023:10.1038/s12276-023-00987-1. [PMID: 37121971 DOI: 10.1038/s12276-023-00987-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 12/20/2022] [Accepted: 02/07/2023] [Indexed: 05/02/2023] Open

Affiliation(s)

Kwangho Kim Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea
Tae Young Ryu Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Eunsun Jung Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Tae-Su Han Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea
Jinkwon Lee Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea
Seon-Kyu Kim Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Yu Na Roh Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea
Moo-Seung Lee Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Cho-Rok Jung Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea
Jung Hwa Lim Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
Ryuji Hamamoto Division of Molecular Modification and Cancer Biology, National Cancer Center, Tokyo, Japan
Hye Won Lee Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea
Keun Hur Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Mi-Young Son Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea. Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.
Dae-Soo Kim Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea.
Hyun-Soo Cho Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. Department of Functional Genomics, Korea University of Science and Technology, Daejeon, Republic of Korea. Department of Biological Science, Sungkyunkwan University, Suwon, Republic of Korea.

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Nian R, Li W, Li X, Zhang J, Li W, Pan F, Cheng J, Jin X. LncRNA MCM3AP-AS1 serves as a competing endogenous RNA of miR-218 to upregulate GLUT1 in papillary thyroid carcinoma. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023;67:55-63. [PMID: 35929906 PMCID: PMC9983800 DOI: 10.20945/2359-3997000000510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]

Go KO, Kim YZ. Brain Invasion and Trends in Molecular Research on Meningioma. Brain Tumor Res Treat 2023;11:47-58. [PMID: 36762808 PMCID: PMC9911709 DOI: 10.14791/btrt.2022.0044] [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: 12/11/2022] [Revised: 01/06/2023] [Accepted: 01/09/2023] [Indexed: 02/05/2023] Open

Gu X, Wang S, Jin B, Qi Z, Deng J, Huang C, Yin X. A pathway analysis-based algorithm for calculating the participation degree of ncRNA in transcriptome. Sci Rep 2022;12:22654. [PMID: 36587048 PMCID: PMC9805457 DOI: 10.1038/s41598-022-27178-8] [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: 05/17/2022] [Accepted: 12/27/2022] [Indexed: 01/01/2023] Open

Affiliation(s)

Xinyi Gu grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Shen Wang grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Bo Jin grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Zhidan Qi grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Jin Deng grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Chen Huang grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China
Xiaofeng Yin grid.411634.50000 0004 0632 4559Department of Orthopedics and Traumatology, Peking University People’s Hospital, Beijing, 100044 China ,2grid.11135.370000 0001 2256 9319Key Laboratory of Trauma and Neural Regeneration (Peking University), Beijing, China

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Wang Y, Li M, Zeng J, Yang Y, Li Z, Hu S, Yang F, Wang N, Wang W, Tie J. MiR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF. Front Immunol 2022;13:1008195. [PMID: 36268034 PMCID: PMC9576935 DOI: 10.3389/fimmu.2022.1008195] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 09/05/2022] [Indexed: 12/24/2022] Open

Abstract

BACKGROUND

Gastric cancer (GC) is one of the most malignant and lethal cancers worldwide. Multiple microRNAs (miRNAs) have been identified as key regulators in the progression of GC. However, the underlying pathogenesis that miRNAs govern GC malignancy remains uncertain. Here, we identified a novel miR-585-5p as a key regulator in GC development.

METHODS

The expression of miR-585-5p in the context of GC tissue was detected by in situ hybridization for GC tissue microarray and assessed by H-scoring. The gain- and loss-of-function analyses comprised of Cell Counting Kit-8 assay and Transwell invasion and migration assay. The expression of downstream microphthalmia-associated transcription factor (MITF), cyclic AMP-responsive element-binding protein 1 (CREB1) and mitogen-activated protein kinase 1 (MAPK1) were examined by Immunohistochemistry, quantitative real-time PCR and western blot. The direct regulation between miR-585-5p and MITF/CREB1/MAPK1 were predicted by bioinformatic analysis and screened by luciferase reporter assay. The direct transcriptional activation of CREB1 on MITF was verified by luciferase reporter assay, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs). The interaction between MAPK1 and MITF was confirmed by co-immunoprecipitation (Co-IP) and immunofluorescent double-labelled staining.

RESULTS

MiR-585-5p is progressively downregulated in GC tissues and low miR-585-5p levels were strongly associated with poor clinical outcomes. Further gain- and loss-of-function analyses showed that miR-585-5p possesses strong anti-proliferative and anti-metastatic capacities in GC. Follow-up studies indicated that miR-585-5p targets the downstream molecules CREB1 and MAPK1 to regulate the transcriptional and post-translational regulation of MITF, respectively, thus controlling its expression and cancer-promoting activity. MiR-585-5p directly and negatively regulates MITF together with CREB1 and MAPK1. According to bioinformatic analysis, promotor reporter gene assays, ChIP and EMSAs, CREB1 binds to the promotor region to enhance transcriptional expression of MITF. Co-IP and immunofluorescent double-labelled staining confirmed interaction between MAPK1 and MITF. Protein immunoprecipitation revealed that MAPK1 enhances MITF activity via phosphorylation (Ser73). MiR-585-5p can not only inhibit MITF expression directly, but also hinder MITF expression and pro-cancerous activity in a CREB1-/MAPK1-dependent manner indirectly.

CONCLUSIONS

In conclusion, this study uncovered miR-585-5p impedes gastric cancer proliferation and metastasis by orchestrating the interactions among CREB1, MAPK1 and MITF.

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Genome-wide CRISPR knockout screening identified G protein pathway suppressor 2 as a novel tumor suppressor for uveal melanoma metastasis. J Cancer Res Clin Oncol 2022:10.1007/s00432-022-04160-5. [PMID: 35941228 DOI: 10.1007/s00432-022-04160-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 06/16/2022] [Indexed: 10/15/2022]

Choi PW, Liu TL, Wong CW, Liu SK, Lum YL, Ming WK. The Dysregulation of MicroRNAs in the Development of Cervical Pre-Cancer—An Update. Int J Mol Sci 2022;23:ijms23137126. [PMID: 35806128 PMCID: PMC9266862 DOI: 10.3390/ijms23137126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/20/2022] [Accepted: 06/24/2022] [Indexed: 02/01/2023] Open

Abstract Globally in 2020, an estimated ~600,000 women were diagnosed with and 340,000 women died from cervical cancer. Compared to 2012, the number of cases increased by 7.5% and the number of deaths increased by 17%. MiRNAs are involved in multiple processes in the pathogenesis of cervical cancer. Dysregulation of miRNAs in the pre-stage of cervical cancer is the focus of this review. Here we summarize the dysregulated miRNAs in clinical samples from cervical pre-cancer patients and relate them to the early transformation process owing to human papillomavirus (HPV) infection in the cervical cells. When HPV infects the normal cervical cells, the DNA damage response is initiated with the involvement of HPV’s E1 and E2 proteins. Later, cell proliferation and cell death are affected by the E6 and E7 proteins. We find that the expressions of miRNAs in cervical pre-cancerous tissue revealed by different studies seldom agreed with each other. The discrepancy in sample types, samples’ HPV status, expression measurement, and methods for analysis contributed to the non-aligned results across studies. However, several miRNAs (miR-34a, miR-9, miR-21, miR-145, and miR-375) were found to be dysregulated across multiple studies. In addition, there are hints that the DNA damage response and cell growth response induced by HPV during the early transformation of the cervical cells are related to these miRNAs. Currently, no review articles analyse the relationship between the dysregulated miRNAs in cervical pre-cancerous tissue and their possible roles in the early processes involving HPV’s protein encoded by the early genes and DNA damage response during normal cell transformation. Our review provides insight on spotting miRNAs involved in the early pathogenic processes and pointing out their potential as biomarker targets of cervical pre-cancer. Collapse

Tian W, Pang X, Luan F. Diagnosis value of miR-181, miR-652, and CA72-4 for gastric cancer. J Clin Lab Anal 2022;36:e24411. [PMID: 35446997 PMCID: PMC9169223 DOI: 10.1002/jcla.24411] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/24/2022] [Accepted: 03/25/2022] [Indexed: 12/01/2022] Open

Mirzajani E, Vahidi S, Norollahi SE, Samadani AA. Novel biomarkers of microRNAs in gastric cancer; an overview from diagnosis to treatment. Microrna 2022;11:12-24. [PMID: 35319404 DOI: 10.2174/2211536611666220322160242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/06/2021] [Accepted: 12/28/2021] [Indexed: 11/22/2022]

Yin T, Zhao H. miR-152-3p impedes the malignant phenotypes of hepatocellular carcinoma by repressing roundabout guidance receptor 1. Cell Mol Biol Lett 2022;27:22. [PMID: 35236289 PMCID: PMC8903719 DOI: 10.1186/s11658-022-00322-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 02/09/2022] [Indexed: 02/08/2023] Open

Nazneen F, Millat MS, Barek MA, Aziz MA, Uddin MS, Jafrin S, Aka TD, Islam MS. Genetic Polymorphism of miR-218-2 (rs11134527) in Cervical Cancer: A Case-Control Study on the Bangladeshi Women. Microrna 2022;10:219-224. [PMID: 34989332 DOI: 10.2174/2211536610666210715102554] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/25/2021] [Accepted: 06/01/2021] [Indexed: 12/24/2022]

Zhang X, Feng WH. Porcine Reproductive and Respiratory Syndrome Virus Evades Antiviral Innate Immunity via MicroRNAs Regulation. Front Microbiol 2022;12:804264. [PMID: 34975824 PMCID: PMC8714953 DOI: 10.3389/fmicb.2021.804264] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022] Open

Madrigal T, Hernández-Monge J, Herrera LA, González-De la Rosa CH, Domínguez-Gómez G, Candelaria M, Luna-Maldonado F, Calderón González KG, Díaz-Chávez J. Regulation of miRNAs Expression by Mutant p53 Gain of Function in Cancer. Front Cell Dev Biol 2021;9:695723. [PMID: 34957087 PMCID: PMC8697023 DOI: 10.3389/fcell.2021.695723] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/15/2021] [Indexed: 12/19/2022] Open

Wei M, Zhang Y, Yang X, Ma P, Li Y, Wu Y, Chen X, Deng X, Yang T, Mao X, Qiu L, Meng W, Zhang B, Wang Z, Han J. Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription. Clin Transl Med 2021;11:e667. [PMID: 34965023 PMCID: PMC8715829 DOI: 10.1002/ctm2.667] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 11/11/2021] [Accepted: 11/17/2021] [Indexed: 02/05/2023] Open

Affiliation(s)

Mingtian Wei Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Yaguang Zhang Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Xuyang Yang Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Pingfan Ma Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Yan Li Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Yangping Wu Department of Respiratory and Critical Care MedicineState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina Department of Clinical Research ManagementWest China HospitalSichuan UniversityChengduChina
Xiangzheng Chen Department of Liver Surgery & Liver Transplantation CenterWest China HospitalSichuan UniversityChengduChina
Xiangbing Deng Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Tinghan Yang Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Xiaobing Mao Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Lei Qiu Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Wenjian Meng Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Bo Zhang Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina
Ziqiang Wang Department of Gastrointestinal SurgeryFrontiers Science Center for Disease‐related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduChina
Junhong Han Research Laboratory of Tumors Epigenetics and GenomicsDepartment of General SurgeryFrontiers Science Center for Disease‐related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina

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Exosome-transmitted circCOG2 promotes colorectal cancer progression via miR-1305/TGF-β2/SMAD3 pathway. Cell Death Discov 2021;7:281. [PMID: 34635639 PMCID: PMC8505430 DOI: 10.1038/s41420-021-00680-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/16/2021] [Accepted: 09/27/2021] [Indexed: 01/10/2023] Open

Dang S, Zhang R, Tian S, Hou P, Li G, Ji M. MicroRNA‑218 inhibits the malignant phenotypes of glioma by modulating the TNC/AKT/AP‑1/TGFβ1 feedback signaling loop. Int J Mol Med 2021;48:205. [PMID: 34558654 PMCID: PMC8480380 DOI: 10.3892/ijmm.2021.5038] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 07/30/2021] [Indexed: 01/22/2023] Open

Abstract

Gliomas are the most malignant and common tumors of the human brain, and the prognosis of glioma patients is extremely poor MicroRNAs (miRNAs or miRs) play critical roles in different types of cancer by performing post-transcriptional regulation of gene expression Although miR-218 has been demonstrated to be decreased in gliomas, its role in gliomas remains largely unknown miR-218 expression was analyzed in gliomas and normal brain tissues (control subjects) using a dataset from The Cancer Genome Atlas A series of in vitro and in vivo studies were performed to determine the biological roles of miR-218 in glioma cells Potential targets of miR-218 were identified using a dual-luciferase reporter system Western blot and dual-luciferase reporter system experiments were performed to evaluate the regulatory effect of miR-218 on the tenascin C (TNC)/AKT/activator protein 1 (AP-1)/transforming growth factor β1 (TGFβ1) pathway It was demonstrated that miR-218 was significantly downregulated in gliomas compared with control subjects, and played potent tumor suppressor roles in glioma cells by inhibiting cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice, as well as inducing cell cycle arrest and apoptosis Mechanistically, miR-218 inhibited malignant phenotypes of glioma cells by binding to the 3′-untranslated region of its target TNC and subsequently suppressing its expression As a result, miR-218 could reduce AKT phosphorylation and subsequently inhibit transcriptional activity of AP-1 by reducing JNK phosphorylation, downregulating the expression of TGFβ1, while TGFβ1 was able to, in turn, activate the TNC/AKT/AP-1 signaling axis Our data revealed a previously unknown tumor suppressor role of miR-218 by blocking the TNC/AKT/AP-1/TGFβ1-positive feedback loop in glioma

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Qu H, Wu S, Li J, Ma T, Li J, Xiang B, Jiang H, Zhang Q. MiR-125b regulates the differentiation of hair follicles in Fine-wool Sheep and Cashmere goats by targeting MXD4 and FGFR2. Anim Biotechnol 2021;34:357-364. [PMID: 34487480 DOI: 10.1080/10495398.2021.1968884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]

Sun JX, Dou GR, Yang ZY, Liang L, Duan JL, Ruan B, Li MH, Chang TF, Xu XY, Chen JJ, Wang YS, Yan XC, Han H. Notch activation promotes endothelial quiescence by repressing MYC expression via miR-218. MOLECULAR THERAPY-NUCLEIC ACIDS 2021;25:554-566. [PMID: 34589277 PMCID: PMC8463319 DOI: 10.1016/j.omtn.2021.07.023] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/26/2021] [Indexed: 11/26/2022]

Affiliation(s)

Jia-Xing Sun State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.,Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Guo-Rui Dou Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Zi-Yan Yang State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Liang Liang State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Juan-Li Duan State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Bai Ruan State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Man-Hong Li Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Tian-Fang Chang Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Xin-Yuan Xu State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Juan-Juan Chen State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Yu-Sheng Wang Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
Xian-Chun Yan State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China
Hua Han State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China

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Cafforio P, Palmirotta R, Lovero D, Cicinelli E, Cormio G, Silvestris E, Porta C, D’Oronzo S. Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls. Cancers (Basel) 2021;13:3968. [PMID: 34439120 PMCID: PMC8394398 DOI: 10.3390/cancers13163968] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/26/2021] [Accepted: 08/03/2021] [Indexed: 12/14/2022] Open

Weidle UH, Birzele F, Brinkmann U, Auslaender S. Gastric Cancer: Identification of microRNAs Inhibiting Druggable Targets and Mediating Efficacy in Preclinical In Vivo Models. Cancer Genomics Proteomics 2021;18:497-514. [PMID: 34183383 DOI: 10.21873/cgp.20275] [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: 03/25/2021] [Revised: 04/30/2021] [Accepted: 05/05/2021] [Indexed: 01/06/2023] Open

Zhang L, Zhang L, Pan Y, Gao J, Xu Y, Li X, Tian Z, Chen H, Wang Y. Downregulation of miR-218 by porcine reproductive and respiratory syndrome virus facilitates viral replication via inhibition of type I interferon responses. J Biol Chem 2021;296:100683. [PMID: 33887325 PMCID: PMC8131720 DOI: 10.1016/j.jbc.2021.100683] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 04/14/2021] [Accepted: 04/18/2021] [Indexed: 12/15/2022] Open

Affiliation(s)

Lin Zhang State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Lu Zhang State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Yu Pan State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Junxin Gao State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Yunfei Xu State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Xi Li State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Zhijun Tian State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Hongyan Chen State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China
Yue Wang State Key Laboratory of Veterinary Biotechnology, National Poultry Laboratory Animal Resource Center, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

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Maleki S, Jabalee J, Garnis C. The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies. Int J Mol Sci 2021;22:4166. [PMID: 33920605 PMCID: PMC8073860 DOI: 10.3390/ijms22084166] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/10/2021] [Accepted: 04/12/2021] [Indexed: 12/22/2022] Open

miR-218-2 regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release. Proc Natl Acad Sci U S A 2021;118:2021770118. [PMID: 33782126 DOI: 10.1073/pnas.2021770118] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open

Zhang S, Cheng Z, Wang Y, Han T. The Risks of miRNA Therapeutics: In a Drug Target Perspective. DRUG DESIGN DEVELOPMENT AND THERAPY 2021;15:721-733. [PMID: 33654378 PMCID: PMC7910153 DOI: 10.2147/dddt.s288859] [Citation(s) in RCA: 138] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/12/2020] [Indexed: 12/18/2022]

Gu D, Ahn SH, Eom S, Lee HS, Ham J, Lee DH, Cho YK, Koh Y, Ignatova E, Jang ES, Chi SW. AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity. MOLECULAR THERAPY. NUCLEIC ACIDS 2021;23:1172-1190. [PMID: 33664996 PMCID: PMC7900643 DOI: 10.1016/j.omtn.2021.01.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 01/20/2021] [Indexed: 02/07/2023]

Xing S, Tian Z, Zheng W, Yang W, Du N, Gu Y, Yin J, Liu H, Jia X, Huang D, Liu W, Deng M. Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1. Mol Cancer 2021;20:9. [PMID: 33407516 PMCID: PMC7786912 DOI: 10.1186/s12943-020-01295-2] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/15/2020] [Indexed: 12/18/2022] Open

Abstract

BACKGROUND

MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC.

METHODS

The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model.

RESULTS

In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo.

CONCLUSIONS

Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

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Affiliation(s)

Shan Xing Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
Zhi Tian Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL, 33612, USA
Wenying Zheng Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Wenjuan Yang Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Nan Du Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
Yixue Gu Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Jiang Yin Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Hao Liu Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Xiaoting Jia Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China
Donglan Huang Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China.
Wanli Liu Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Min Deng Affiliated Cancer Hosipital & Institute of Guangzhou Medical University, Guangzhou Key Laboratory of "Translational Medicine on Malignant Tumor Treatment", No.78, Hengzhigang Road, Guangzhou, 510095, China.

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Chen Y, Yang JL, Xue ZZ, Cai QC, Hou C, Li HJ, Zhao LX, Zhang Y, Gao CW, Cong L, Wang TZ, Chen DM, Li GS, Luo SQ, Yao Q, Yang CJ, Zhu QS, Cao CH. Effects and mechanism of microRNA‑218 against lung cancer. Mol Med Rep 2020;23:28. [PMID: 33179084 PMCID: PMC7673340 DOI: 10.3892/mmr.2020.11666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 07/08/2020] [Indexed: 12/22/2022] Open

Abstract

Lung cancer is the most prevalent and observed type of cancer in Xuanwei County, Yunnan, South China. Lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microRNA (miR)‑218 functions as a tumor suppressor in multiple types of cancer. However, the role of miR‑218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of miR‑218 in XWLC‑05 cells were markedly lower compared with those in immortalized lung epithelial BEAS‑2B cells. The present study also demonstrated that overexpression of miR‑218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWLC‑05 and NSCLC cell line NCI‑H157. Additionally, the results revealed that overexpression of miR‑218 could induce XWLC‑05 and NCI‑H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of miR‑218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B‑cell lymphoma 2 (BCL‑2) and BMI1 proto‑oncogene, polycomb ring finger (BMI‑1) at the mRNA and protein level in XWLC‑05 and NCI‑H157 cell lines. However, we did not observe any remarkable difference in the roles of miR‑218 and miR‑218‑mediated regulation of BCL‑2, BMI‑1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. In conclusion, miR‑218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL‑2 and BMI‑1 in Xuanwei lung cancer. The results demonstrated that miR‑218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of miR‑218 may be a novel approach for the treatment of Xuanwei lung cancer.

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Zhang Y, Zheng Y, Pan E, Zhao C, Zhang H, Liu R, Wang S, Pu Y, Yin L. Synergism of HPV and MNNG repress miR-218 promoting Het-1A cell malignant transformation by targeting GAB2. Toxicology 2020;447:152635. [PMID: 33189795 DOI: 10.1016/j.tox.2020.152635] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/09/2020] [Accepted: 11/10/2020] [Indexed: 12/11/2022]

Wang Y, Jiang Y, Chen L. Role of miR-218-GREM1 axis in epithelial-mesenchymal transition of oral squamous cell carcinoma: An in vivo and vitro study based on microarray data. J Cell Mol Med 2020;24:13824-13836. [PMID: 33107676 PMCID: PMC7754042 DOI: 10.1111/jcmm.15972] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 09/13/2020] [Accepted: 09/18/2020] [Indexed: 12/13/2022] Open

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent cancer that develops in the head and neck area and has high annual mortality despite optimal treatment. microRNA‐218 (miR‐218) is a tumour inhibiting non‐coding RNA that has been reported to suppress the cell proliferation and invasion in various cancers. Thus, our study aims to determine the mechanism underlying the inhibitory role of miR‐218 in OSCC. We conducted a bioinformatics analysis to screen differentially expressed genes in OSCC and their potential upstream miRNAs. After collection of surgical OSCC tissues, we detected GREM1 expression by immunohistochemistry, RT‐qPCR and Western blot analysis, and miR‐218 expression by RT‐qPCR. The target relationship between miR‐218 and GREM1 was assessed by dual‐luciferase reporter gene assay. After loss‐ and gain‐of‐function experiments, OSCC cell proliferation, migration and invasion were determined by MTT assay, scratch test and Transwell assay, respectively. Expression of TGF‐β1, Smad4, p21, E‐cadherin, Vimentin and Snail was measured by RT‐qPCR and Western blot analysis. Finally, effects of miR‐218 and GREM1 on tumour formation and liver metastasis were evaluated in xenograft tumour‐bearing nude mice. GREM1 was up‐regulated, and miR‐218 was down‐regulated in OSCC tissues, and GREM1 was confirmed to be the target gene of miR‐218. Furthermore, after up‐regulating miR‐218 or silencing GREM1, OSCC cell proliferation, migration and invasion were reduced. In addition, expression of TGF‐β signalling pathway‐related genes was diminished by overexpressing miR‐218 or down‐regulating GREM1. Finally, up‐regulated miR‐218 or down‐regulated GREM1 reduced tumour growth and liver metastasis in vivo. Taken together, our findings suggest that the overexpression of miR‐218 may inhibit OSCC progression by inactivating the GREM1‐dependent TGF‐β signalling pathway.

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Yang KK, Xu HM, Huang JY, Guo YX, Wang ZN. Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer. Technol Cancer Res Treat 2020;19:1533033819901126. [PMID: 32019439 PMCID: PMC7003157 DOI: 10.1177/1533033819901126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open

Lin J, Zhang Y, Zeng X, Xue C, Lin X. CircRNA CircRIMS Acts as a MicroRNA Sponge to Promote Gastric Cancer Metastasis. ACS OMEGA 2020;5:23237-23246. [PMID: 32954174 PMCID: PMC7495717 DOI: 10.1021/acsomega.0c02991] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Accepted: 08/17/2020] [Indexed: 06/11/2023]

Mu L, Guan B, Tian J, Li X, Long Q, Wang M, Wang W, She J, Li X, Wu D, Du Y. MicroRNA‑218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2. Oncol Rep 2020;44:1961-1970. [PMID: 32901879 PMCID: PMC7551166 DOI: 10.3892/or.2020.7759] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 08/05/2020] [Indexed: 02/06/2023] Open

Yu J, Zhou Z, Wei Z, Wu J, OuYang J, Huang W, He Y, Zhang C. FYN promotes gastric cancer metastasis by activating STAT3-mediated epithelial-mesenchymal transition. Transl Oncol 2020;13:100841. [PMID: 32763503 PMCID: PMC7408597 DOI: 10.1016/j.tranon.2020.100841] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/01/2020] [Accepted: 07/19/2020] [Indexed: 12/24/2022] Open

Sherchan P, Travis ZD, Tang J, Zhang JH. The potential of Slit2 as a therapeutic target for central nervous system disorders. Expert Opin Ther Targets 2020;24:805-818. [PMID: 32378435 PMCID: PMC7529836 DOI: 10.1080/14728222.2020.1766445] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 05/05/2020] [Indexed: 10/24/2022]

Zhao H, Yan G, Zheng L, Zhou Y, Sheng H, Wu L, Zhang Q, Lei J, Zhang J, Xin R, Jiang L, Zhang X, Chen Y, Wang J, Xu Y, Li D, Li Y. STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma. Theranostics 2020;10:6483-6499. [PMID: 32483465 PMCID: PMC7255033 DOI: 10.7150/thno.44025] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/21/2020] [Indexed: 02/06/2023] Open

Abstract

Background: Cancer cells undergoing invasion and metastasis possess a phenotype with attenuated glycolysis, but enhanced fatty acid oxidation (FAO). Calcium (Ca²⁺)-mediated signaling pathways are implicated in tumor metastasis and metabolism regulation. Stromal-interaction molecule 1 (STIM1) triggered store-operated Ca²⁺ entry (SOCE) is the major route of Ca²⁺ influx for non-excitable cells including hepatocellular carcinoma (HCC) cells. However, whether and how STIM1 regulates the invasion and metastasis of HCC via metabolic reprogramming is unclear.

Methods: The expressions of STIM1 and Snail1 in the HCC tissues and cells were measured by immunohistochemistry, Western-blotting and quantitative PCR. STIM1 knockout-HCC cells were generated by CRISPR-Cas9, and gene-overexpression was mediated via lentivirus transfection. Besides, the invasive and metastatic activities of HCC cells were assessed by transwell assay, anoikis rate in vitro and lung metastasis in vivo. Seahorse energy analysis and micro-array were used to evaluate the glucose and lipid metabolism.

Results: STIM1 was down-regulated in metastatic HCC cells rather than in proliferating HCC cells, and low STIM1 levels were associated with poor outcome of HCC patients. During tumor growth, STIM1 stabilized Snail1 protein by activating the CaMKII/AKT/GSK-3β pathway. Subsequently, the upregulated Snail1 suppressed STIM1/SOCE during metastasis. STIM1 restoration significantly diminished anoikis-resistance and metastasis induced by Snail1. Mechanistically, the downregulated STIM1 shifted the anabolic/catabolic balance, i.e., from aerobic glycolysis towards AMPK-activated fatty acid oxidation (FAO), which contributed to Snail1-driven metastasis and anoikis-resistance.

Conclusions: Our data provide the molecular basis that STIM1 orchestrates invasion and metastasis via reprogramming HCC metabolism.

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