Abstract The morbidity of lung cancer ranks first among all cancers. Lung adenocarcinoma (LUAD) is a classification of lung cancer, and cell invasion and migration of LUAD are the main causes for its high mortality. Therefore, further exploring the potential mechanism of LUAD metastasis may provide bases for following targeted drug development and treatment of LUAD. In this study, clinical data as well as gene expression profiles were obtained from TCGA-LUAD and GEO to analyze CTHRC1 expression. The result found that CTHRC1 was significantly high in LUAD. Similar results were also discovered in 4 cancer cell lines. Moreover, overexpressed/knock-down CTHRC1 cell lines were constructed. It was uncovered that overexpressing CTHRC1 promoted LUAD cell migration and invasion, and inhibited cell adhesion, while knocked down CTHRC1 had the opposite effect. Afterward, the upstream miRNAs that regulated CTHRC1 were predicted by several bioinformatics websites. It was testified by dual-luciferase method that CTHRC1 was negatively mediated by miR-30a-5p. Overexpressed miR-30a-5p suppressed cell invasion/migration, and increased cell adhesion, while overexpressing CTHRC1 as well reversed such impacts. In conclusion, it was disclosed in this study that CTHRC1 worked as a cancer promoter in LUAD, and miR-30a-5p could target and downregulate CTHRC1 to regulate cell adhesion, and inhibited LUAD cell invasion and migration. These results elucidated at cellular level that upregulated CTHRC1 may be a marker protein for LUAD metastasis. Supplementary Information The online version contains supplementary material available at 10.1186/s13019-022-01788-9. Keywords: LUAD, CTHRC1, miR-30a-5p, Invasion and migration, Cell adhesion Introduction Lung cancer is a recognized human health killer, with its mortality ranks first among all cancers for several years (about 11.6% in 2018) and its morbidity is relatively high [[39]1]. After years of research, lung cancer is divided into many subtypes, one of which is lung adenocarcinoma (LUAD). Over 500,000 people died from lung cancer every year, and the amount has been significantly increasing over the past few decades [[40]2–[41]4]. Although great efforts have been devoted to developing new treatment of lung cancer in recent years, the prognosis of malignant patients remains poor with a 5-year survival rate less than 10% [[42]5, [43]6]. Shortage of understanding of LUAD-related biological mechanism limits the improvement of therapeutic effect. Hence, it is important to dig related genes of LUAD occurrence and development, and explore its effective mechanism for increasing clinical efficacy. CTHRC1 is a chondrocyte-secreted glycoprotein first found in the rat balloon-injured artery model and can inhibit collagen matrix synthesis [[44]7, [45]8]. As revealed in recent years, CTHRC1 is upregulated in various tumors, and promote cancer cell invasion and migration [[46]9–[47]11], which also works as a potential biomarker of various cancers. For example, MEI ZHENG et al. [[48]12] disclosed that CTHRC1 overexpression promotes cervical cancer development by simulating Wnt/PCP signaling pathway. Moreover, upregulated CTHRC1 promotes the invasion of epithelial ovarian cancer via stimulating EGFR signaling pathway. However, CTHRC1 high expression in LUAD might pertain to the angiogenesis of LUAD and indicate poor prognosis of LUAD [[49]13]. But reasons for high expression of CTHRC1 and its regulatory mechanism in LUAD are not clear. Effects of miRNAs in vivo have been neglected for a long time. However, recent study represented that miRNA mediates gene expression via targeting 3’-untranslated region (UTR) of mRNA [[50]14], so as to modulate the progression of various diseases. Studies revealed that CTHRC1 is regulated by miRNAs in cancers. For example, miR-155 targets CTHRC1 to inhibit colorectal cancer [[51]15]. MiR-30c-mediated CTHRC1 accelerates the metastasis of LUAD cells [[52]16]. MiR-98 targets CTHRC1 to suppress liver cancer cell progression [[53]17]. Nonetheless, there are no reports alike in LUAD. This work scrutinized CTHRC1 and LUAD occurrence and development, and uncovered the molecular mechanism of miRNA targeting CTHRC1, which offers researching directions for targeted treatment of LUAD. Materials and methods Bioinformatics method LUAD related data sets were acquired from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), as shown in Table [54]1. Expression differences of CTHRC1 between normal tissue and LUAD tissue were tested by t-test, and the effect of CTHRC1 expression on patient’s prognosis was detected with R “survival” package. Upstream miRNAs that regulated CTHRC1 were predicted with starBase, TargetScan, miRDB and mirDIP databases, and verified via Pearson correlation analysis. Pathway enrichment analysis was undertaken on CTHRC1 by using Gene Set Enrichment Analysis (GSEA) software. Table 1. Sample information related to LUAD of Data Sets from GEO and TCGA databases Data set Data type Normal Tumor Follow-up [55]GSE31210 mRNA 20 226 Yes [56]GSE32863 mRNA 58 58 No [57]GSE43458 mRNA 30 80 No [58]GSE72094 mRNA 0 442 Yes [59]GSE75037 mRNA 83 83 No [60]GSE116959 mRNA 11 57 No [61]GSE119269 miRNA/mRNA 0/0 155/155 No TCGA-LUAD miRNA/mRNA 46/59 521/535 Yes [62]Open in a new tab Cell culture and transfection LUAD cell lines H1650 (BNCC100260), Calu-3 (BNCC338514), A549 (BNCC337696), H1975 (BNCC100301), and human bronchial epithelial cell line BEAS-2B (BNCC338205) were bought from BeNa Culture Collection. All cells were kept in Roswell Park Memorial Institute (RPMI)-1640 (Thermo Fisher Scientific Company, Waltham, Massachusetts, USA) medium containing 5% fetal bovine serum (FBS), and cultured in an incubator under general conditions. NC mimic, miR-30a-5p mimic (mimic) were offered by GenePharma (Shanghai, China). oe-CTHRC1 vector, 3 si-CTHRC1 vectors and their negative control lentivirus packing vectors were acquired from Invitrogen (Carlsbad, CA, USA). Vectors were transiently transfected into Calu-3 cells with Lipofectamine 2000 (Thermo Fisher Scientific, Inc.). All cells were cultivated for at least 24 h in the complete medium before transfection, and collected after 36–48 h of transfection. qRT-PCR Total RNA was separated with TRIzol Reagent (Invitrogen). MRNA was reversely transcribed into cDNA with M-MLV Reverse Transcriptase Kit (TaKaRa). MiRNA was reversely transcribed with Superscript II Kit (Invitrogen). PCR system was constructed with miScript SYBR Green PCR Kit (Qiagen, Hilden, Germany). Applied Biosystems 7300 Real-Time PCR System (Applied Biosystems, USA) was applied for qRT-PCR to detect gene expression level, with U6 and GAPDH as the internal references.