C1632 suppresses the migration and proliferation of non-small-cell lung cancer cells involving LIN28 and FGFR1 pathway.
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ABSTRACT:
SUBMITTER: Chen JY
PROVIDER: S-EPMC8743659 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis study investigated the functions of FAM46B in non-small cell lung cancer (NSCLC) cells and determined the role of β-catenin/matrix metalloproteinase 7 (MMP7) signaling in mediating these functions.MethodsHuman paracancerous and cancer tissues were collected from lung cancer patients. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay while migration and invasion were examined by transwell chamber assays. Relative mRNA expression and protein levels were determined by quantitative reverse transcription (q-RT) polymerase chain reaction (PCR) and western blot, respectively.ResultsFAM46B displayed reduced expression in lung cancer tissues compared with paired paracancerous tissues. In contrast, β-catenin protein levels were elevated in lung cancer tissues compared with paired paracancerous tissues. FAM46B over-expression reduced proliferation, migration and invasion of A549 and H292 cells, as well as decreased the protein levels of β-catenin, MMP7 and vascular endothelial growth factor (VEGF). On the other hand, FAM46B knockdown by shRNA in H1975 cells enhanced proliferation, migration and invasion, as well as increased the protein levels of β-catenin and MMP7. These enhanced effects were ameliorated by treatment with the Wnt/β-catenin inhibitor XAV939, suggesting a role for Wnt signaling in mediating the functions of FAM46B in NSCLC.ConclusionsFAM46B functions as a tumor suppressor by inhibiting β-catenin/MMP7 signaling.
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Project description:PurposeRecent studies have determined that long non-coding RNAs (lncRNAs) are potential prognostic biomarkers for non-small cell lung cancers (NSCLCs). The purpose of this study was to analyze the function and associated pathways of zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) in NSCLC cells.MethodsWe used qRT-PCR to analyze ZFPM2-AS1's transcription level. Its proliferation, migration, and invasion capacities were determined using MTT, colony forming, wound healing, and transwell assays. We additionally analyzed the correlation between ZFPM2 and immune infiltration using the Tumor Immune Estimation Resource (TIMER) database, and the protein expression levels using Western blots.ResultsWe found that ZFPM2-AS1 expression in NSCLC specimens and cell lines was elevated compared to the control group. ZFPM2-AS1 is an oncogene and independent prognostic predictor of poor survival in NSCLCs, and its expression had a positive correlation with tumor size and lymph node metastasis in our clinical data. MTT, colony forming, wound healing, and transwell assays showed a positive correlation between ZFPM2-AS1 expression and the proliferation, migration, and invasion of NSCLC cells in the presence and absence of interferon- (IFN-γ). Using the TIMER database, we hypothesized that ZFPM2 was negatively correlated with ZFPM2-AS1 expression, as well as the immune infiltration levels in lung adenocarcinoma (LUAD). Finally, we found that ZFPM2-AS1 negatively regulated ZFPM2 expression, and had a positive correlation with PD-L1 expression through the JAK-STAT and AKT pathways.ConclusionOur study confirmed that ZFPM2-AS1 promotes the proliferation, migration, and invasion of NSCLC cells via the JAK-STAT and AKT pathways. Further research on the ZFPM2-AS1 pathway regulation mechanism is needed.
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