title: miR-130a regulates macrophage polarization and is associated with non-small cell lung cancer.
abstract: Lung cancer is the most common cancer as well as the leading cause of cancer-related mortalities worldwide. Macrophages are the most abundant immune cells in primary and metastatic tumors, and contribute to tumor initiation, progression and metastasis. Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. In the present study, we investigated a pivotal role of miR-130a in macrophage polarization and whether it was associated with poor prognosis in non-small cell lung cancer (NSCLC), using RT-qPCR and western blot analyses. The in vitro experiments showed that miRNA-130a was expressed at a higher level in M1 compared to M2 macrophages. The enforced expression of miR-130a in macrophages resulted in a significantly increased production of proinflammatory cytokines, whereas deletion of miR-130a impaired the M2‑associated gene expression and led to an M1-biased response. Mechanistically, the bioinformatics analysis revealed that proliferator-activated receptor γ (PPARγ) is a potential target of miR-130a. Additionally, the luciferase assay confirmed that PPARγ translation was suppressed by miR-130a through the interaction with the 3'UTR of PPARγ mRNA. A subsequent analysis revaled that the induction of miR-130a suppressed PPARγ protein expression. In NSCLC patients, the results showed that miR-130a downregulation exhibited clinical relevance as it was correlated with poor prognosis and increased tumor stage and metastasis. In addition, miR‑130a was inversely correlated with the macrophage marker, CD163, and target gene, PPARγ. Taken together, the results established miR-130a as a molecular switch during macrophage development and as a potential target for the treatment of NSCLC.
authors.affiliation: Department of Medical Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Thoracic Surgery, Peking University, First Hospital, Beijing 100034, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Medical Oncology, Cancer Hospital Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D012333:RNA, Messenger; D011956:Receptors, Cell Surface