ArticleCancer science2017
Thyroid transcription factor-1-regulated microRNA-532-5p targets KRAS and MKL2 oncogenes and induces apoptosis in lung adenocarcinoma cells.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- miR-542-3p targets TTF1 to regulate proliferation, invasion, and migration of lung adenocarcinoma via the MAPK signaling pathway.Scientific reports · 2026Article
- Systematic gene expression analysis of putative target genes linked to miR-31 in 83 oral squamous cell carcinoma samples.Head & face medicine · 2025Article
- Circular RNAs: a small piece in the heart failure puzzle.Functional & integrative genomics · 2024Review
- Differential microRNA expression for diagnosis and prognosis of papillary thyroid cancer.Frontiers in medicine · 2023Review
- TTF1 suppresses neuroblastoma growth and induces neuroblastoma differentiation by targeting TrkA and the miR-204/TrkB axis.iScience · 2022Article
- Transcription start site-level expression of thyroid transcription factor 1 isoforms in lung adenocarcinoma and its clinicopathological significance.The journal of pathology. Clinical research · 2021Article
- Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development and identifies novel HIF-1α regulator.Cancer science · 2021Article
- Use of miR‑145 and testicular nuclear receptor 4 inhibition to reduce chemoresistance to docetaxel in prostate cancer.Oncology reports · 2021Article
- NKX2-1 re-expression induces cell death through apoptosis and necrosis in dedifferentiated thyroid carcinoma cells.PloS one · 2021Article
- Neuroprotective effects of miR-532-5p against ischemic stroke.Metabolic brain disease · 2020Article
- MicroRNA-532-5p is implicated in the regulation of osteoporosis by forkhead box O1 and osteoblast differentiation.BMC musculoskeletal disorders · 2020Article
- Review
- MiRNA-532-5p Regulates CUMS-Induced Depression-Like Behaviors and Modulates LPS-Induced Proinflammatory Cytokine Signaling by Targeting STAT3.Neuropsychiatric disease and treatment · 2020Article
- A Circular RNA Derived from Golgi Glycoprotein 1 mRNA RegulatesOncoTargets and therapy · 2020Article
- MicroRNA-532 exerts oncogenic functions in t(4;14) multiple myeloma by targeting CAMK2N1.Human cell · 2019Article
- Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction.The EMBO journal · 2019Article
- Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression.Archives of endocrinology and metabolism · 2019Review
- MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis.British journal of cancer · 2018Article
- Identification of differential protein-coding gene expressions in early phase lung adenocarcinoma.Thoracic cancer · 2018Article
- microRNA-532 suppresses the PI3K/Akt signaling pathway to inhibit colorectal cancer progression by directly targeting IGF-1R.American journal of cancer research · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thyroid transcription factor-1 (TTF-1), also known as NKX2-1, plays a role as a lineage-survival oncogene in lung adenocarcinoma that possesses double-edged sword characteristics. Although evidence from previous studies has steadily accumulated regarding the roles of TTF-1 in transcriptional regulation of protein-coding genes, little is known about its regulatory relationship with microRNAs. Here, we utilized an integrative approach designed to extract maximal information from expression profiles of both patient tumors in vivo and TTF-1-inducible cell lines in vitro, which identified microRNA (miR)-532-5p as a novel transcriptional target of TTF-1. We found that miR-532-5p is directly regulated by TTF-1 through its binding to a genomic region located 8 kb upstream of miR-532-5p, which appears to impose transcriptional regulation independent of that of CLCN5, a protein-coding gene harboring miR-532-5p in its intron 3. Furthermore, our results identified KRAS and MKL2 as novel direct targets of miR-532-5p. Introduction of miR-532-5p mimics markedly induced apoptosis in KRAS-mutant as well as KRAS wild-type lung adenocarcinoma cell lines. Interestingly, miR-532-5p showed effects on MEK-ERK pathway signaling, specifically in cell lines sensitive to siKRAS treatment, whereas those miR-532-5p-mediated effects were clearly rendered as phenocopies by repressing expression or inhibiting the function of MKL2 regardless of KRAS mutation status. In summary, our findings show that miR-532-5p is a novel transcriptional target of TTF-1 that plays a tumor suppressive role by targeting KRAS and MKL2 in lung adenocarcinoma.
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