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Long Noncoding RNA KCNQ1OT1 Promotes the Progression of Non-Small Cell Lung Cancer via Regulating miR-204-5p/ATG3 Axis
| Content Provider | Scilit |
|---|---|
| Author | Kang, Yan Jia, Yaoli Wang, Qilong Zhao, Qianru Song, Meng Ni, Ran Wang, Jing |
| Copyright Year | 2019 |
| Description | Journal: OncoTargets and therapy Purpose: Non-small cell lung cancer (NSCLC) is the first leading cause of cancer-related death globally. Long noncoding RNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was involved in the progression of multiple cancers by sponging target miRNA. We aimed to explore the pathological mechanism of KCNQ1OT1 in NSCLC progression. Methods: The expression of KCNQ1OT1, miR-204-5p and autophagy-related gene 3 (ATG3) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry assay were conducted for the detection of cell proliferation and apoptosis, respectively. Western blot assay was performed to examine the protein levels of B-cell lymphoma-2 (BCL-2), BCL2-Associated X (Bax), cleaved caspase-3, cleaved caspase-9 and LC3Ⅱ/LC3Ⅰ and P62. The interaction between miR-204-5p and KCNQ1OT1 or ATG3 was validated by dual-luciferase reporter system and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to explore the function of KCNQ1OT1 in vivo. Immunohistochemistry (IHC) staining assay was used for the analysis of ki67-positive cell percentage. Results: The expression of KCNQ1OT1 and ATG3 was up-regulated whereas miR-204-5p was down-regulated in NSCLC tumors and cells. MiR-204-5p was inversely correlated with KCNQ1OT1 or ATG3. In addition, KCNQ1OT1 knockdown facilitated apoptosis, inhibited autophagy and proliferation of NSCLC cells in vitro and blocked tumor growth in vivo. However, the miR-204-5p inhibitor reversed the effects. More importantly, ATG3 was a target gene of miR-204-5p and ATG3 overexpression restored the effect of miR-204-5p on NSCLC cell progression. Conclusion: KCNQ1OT1 promotes cell proliferation and autophagy and inhibits cell apoptosis via regulating miR-204-5p/ATG3 axis, providing a promising target for NSCLC therapy. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911321/pdf https://www.dovepress.com/getfile.php?fileID=54590 |
| Ending Page | 10797 |
| Page Count | 11 |
| Starting Page | 10787 |
| ISSN | 11786930 |
| DOI | 10.2147/ott.s226044 |
| Journal | OncoTargets and therapy |
| Volume Number | ume 12 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2019-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: OncoTargets and therapy |
| Content Type | Text |
| Subject | Pharmacology (medical) Oncology |
