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This study compares noncancerous and lung adenocarcinoma samples for HIF-1α, miR-210-3p, and CCL2, then tests lung adenocarcinoma cell lines and 3D spheroids. HIF-1α stabilization elevates miR-210-3p and suppresses CCL2, impairing monocyte infiltration. miR-210-3p directly binds the CCL2 3′UTR, and miR-210-3p inhibition promotes antitumor M1 recruitment and tumor regression in a xenograft zebrafish model.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hypoxia-induced-mir-210-3p-expression-in-lung-adenocarcinoma-potentiates-tumor-development-by-regulating-ccl2-mediated-monocyte-infiltration/330595/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/hypoxia-induced-mir-210-3p-expression-in-lung-adenocarcinoma-potentiates-tumor-development-by-regulating-ccl2-mediated-monocyte-infiltration/330595.png","ImageObject",300,407,{"name":92,"@type":93},"Aurora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does hypoxia influence miR-210-3p and CCL2 in lung adenocarcinoma?","Question",{"text":113,"@type":114},"HIF-1α stabilization under hypoxic conditions increases miR-210-3p levels while inhibiting CCL2 expression. This establishes a functional link between hypoxia and the CCL2-mediated immune recruitment axis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What is the mechanism by which miR-210-3p regulates CCL2?",{"text":118,"@type":114},"miR-210-3p directly binds the 3′UTR of CCL2 mRNA and silences it. Suppressing miR-210-3p substantially reverses the hypoxia-driven changes in CCL2 expression.",{"name":120,"@type":111,"acceptedAnswer":121},"What happens to monocyte infiltration and macrophage phenotype when miR-210-3p is inhibited?",{"text":122,"@type":114},"Inhibition of miR-210-3p restores monocyte migration in cells with altered HIF-1α activity. In 3D tumor spheroids, miR-210-3p inhibition promotes monocyte recruitment and skewing toward an antitumor M1 phenotype.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},330595,1790829048,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},4810365810221,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Hypoxia-induced miR-210-3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2 mediated monocyte infiltration Leena Arora 1, Debarun Patra 1, Soumyajit Roy 1, Sidhanta Nanda 1 , Navneet Singh2, Anita K. Verma3, Anuradha Chakraborti4 , Suman Dasgupta5  and Durba Pal 1   \n1 Department of Biomedical Engineering, Indian Institute of Technology Ropar, Punjab, India  \n2 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India  \n3 Department of Zoology, Kirori Mal College, University of Delhi, India  \n4 Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India  \n5 Department of Molecular Biology & Biotechnology, Tezpur University, Assam, India  \nKeywords  \nCCL2; HIF-1Α; LUAD; miR-210-3p; monocyte infiltration  \nCorrespondence  \nD. Pal, Department of Biomedical Engineering, Indian Institute of Technology Ropar, Rupnagar 140001, Punjab, India Tel: +91 01881 23 2506  \nE-mail: [durba.pal@iitrpr.ac.in](durba.pal@iitrpr.ac.in)  \n(Received 16 December 2021, revised 24 April 2022, accepted 2 June 2022, available online 22 March 2024)  \ndoi:10 . 1002/1878-0261 .13260  \nIn most cancers, tumor hypoxia downregulates the expression of C-C motif chemokine 2 (CCL2), and this downregulation has been implicated in monocyte infiltration and tumor progression; however, the molecular mechanism is not yet clear. We compared noncancerous and lungadenocarcinoma human samples for hypoxia-inducible factor 1-alpha (HIF-1A), microRNA-210-3p (mir-210-3p), and CCL2 levels. Mechanistic studies were performed on lung adenocarcinoma cell lines and 3D tumor spheroids to understand the role of hypoxia-induced miR-210-3p in the regulation of CCL2 expression and macrophage polarization. HIF-1Α stabilization increases miR-210-3p levels in lung adenocarcinoma and impairs monocyte infiltration by inhibiting CCL2 expression. Mechanistically, miR- 210-3p directly binds to the 30untranslated region (UTR) of CCL2 mRNA and silences it. Suppressing miR-210-3p substantially downregulates the effect of hypoxia on CCL2 expression. Monocyte migration is significantly hampered in miR-210-3p mimic-transfected HIF-1A silenced cancer cells. In contrast, inhibition of miR-210-3p in HIF-1A-overexpressed cells markedly restored monocyte migration, highlighting a direct link between the miR- 210-3p level and tumor monocyte burden. Moreover, miR-210-3p inhibition in 3D tumor spheroids promotes monocyte recruitment and skewing towards an antitumor M1 phenotype. Anti-hsa-miR-210-3p-locked nucleic acid (LNA) delivery in a lung tumor xenograft zebrafish model caused tumor regression, suggesting that miR-210-3p could be a promising target for immunomodulatory therapeutic strategies against lung adenocarcinoma.  \nAbbreviations  \n30 UTR, 30 untranslated region; 5-Aza, 5-Aza-20-deoxycytidine; 5mC, 5-methylcytosine; AhR, aryl hydrocarbon receptor; ARNT, AhR nuclear translocator; CCL2, CC chemokine ligand 2; CCR2, C-C chemokine receptor type 2; CD, cluster of differentiation; cDNA, complementary deoxyribonucleic acid; CoCl2, cobalt chloride; DAPI, 40 ,6-diamidino-2-phenylindole; DNMT, DNA N-methyl transferase; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HIF-1Α, hypoxia inducible factor-1Α; HRE, hypoxia response element; HUVEC, human umbilical vein endothelial cell; Hypoxa miR, hypoxia-associated microRNA; IL, interleukin; LNA, locked nucleic acid; LUAD, lung adenocarcinoma; miR-210-3p, microRNA-210-3p; MPEG1 . 1, macrophage expressed 1-tandem duplicate 1; MPX, myeloid-specificperoxidase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NCCS, National Centre for Cell Science; NSCLC, non-small-cell lung cancer; OCT, optimal cutting temperature; ODDD, oxygen-dependent death domain; OE, overexpression; PER, period circadian protein; PHD, prolyl hydroxylase domain; pVHL, protein Von","cbCaii8Vo8OJI8z0","https://ap.wps.com/l/cbCaii8Vo8OJI8z0","pdf",6755703,23,"English","# Introduction\n## Hypoxia, lung adenocarcinoma, and tumor-associated macrophages\n# Mechanistic Findings (HIF-1α/miR-210-3p/CCL2)\n## Effects on monocyte infiltration and macrophage polarization\n# Therapeutic Implications\n## miR-210-3p targeting in xenograft model\n# Abbreviations","[{\"question\":\"How does hypoxia influence miR-210-3p and CCL2 in lung adenocarcinoma?\",\"answer\":\"HIF-1α stabilization under hypoxic conditions increases miR-210-3p levels while inhibiting CCL2 expression. This establishes a functional link between hypoxia and the CCL2-mediated immune recruitment axis.\"},{\"question\":\"What is the mechanism by which miR-210-3p regulates CCL2?\",\"answer\":\"miR-210-3p directly binds the 3′UTR of CCL2 mRNA and silences it. Suppressing miR-210-3p substantially reverses the hypoxia-driven changes in CCL2 expression.\"},{\"question\":\"What happens to monocyte infiltration and macrophage phenotype when miR-210-3p is inhibited?\",\"answer\":\"Inhibition of miR-210-3p restores monocyte migration in cells with altered HIF-1α activity. In 3D tumor spheroids, miR-210-3p inhibition promotes monocyte recruitment and skewing toward an antitumor M1 phenotype.\"}]","Hypoxia-induced miR-210-3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2 mediated monocyte infiltration | PDF",1789989494,58]