The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1
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Purpose: The goal of this study was to explore the effects of hsa-let-7g on cell proliferation and apoptosis, and elucidate its role inlung cancer development. Materials and Methods: The expression levels of has-let-7g and HOXB1 in tissues and cells were measured by qRT-PCR. An inhibitorof hsa-let-7g or one targeting a control messenger RNA were transfected into A549 and H1944 lung cancer cells, and the effects ofhsa-let-7g dysregulation on cell viability and apoptosis were analyzed using CCK-8 and apoptosis detection assays. HOXB1 was confirmedas the target gene of hsa-let-7g, based on luciferase reporter assay results. The relationship between hsa-let-7g and HOXB1was confirmed by co-transfection of inhibitors of hsa-let-7g and HOXB1 followed by Western blot, CCK-8, and apoptosis detectionassays. Results: We observed high expression of hsa-let-7g in lung cancer tissues compared to the corresponding normal tissues, andgenerally higher expression of hsa-let-7g in patients with advanced tumor classification. The results of CCK-8 and apoptosis detectionexperiments showed that the inhibition of hsa-let-7g significantly inhibited proliferation of A549 and H1944 cells, but also promotedapoptosis. HOXB1 is a specific target of hsa-let-7g, and downregulation of HOXB1 in lung cancer cells reversed the suppressiveeffects caused by knocking down hsa-let-7g. Conclusion: These data collectively suggest that the expression of hsa-let-7g inhibits lung cancer cells apoptosis and promotesproliferation by down-regulating HOXB1. The results from this study demonstrate the potential of hsa-let-7g/HOXB1 axis as atherapeutic target for the treatment of lung cancer.
Abstract
Purpose: The goal of this study was to explore the effects of hsa-let-7g on cell proliferation and apoptosis, and elucidate its role inlung cancer development. Materials and Methods: The expression levels of has-let-7g and HOXB1 in tissues and cells were measured by qRT-PCR. An inhibitorof hsa-let-7g or one targeting a control messenger RNA were transfected into A549 and H1944 lung cancer cells, and the effects ofhsa-let-7g dysregulation on cell viability and apoptosis were analyzed using CCK-8 and apoptosis detection assays. HOXB1 was confirmedas the target gene of hsa-let-7g, based on luciferase reporter assay results. The relationship between hsa-let-7g and HOXB1was confirmed by co-transfection of inhibitors of hsa-let-7g and HOXB1 followed by Western blot, CCK-8, and apoptosis detectionassays. Results: We observed high expression of hsa-let-7g in lung cancer tissues compared to the corresponding normal tissues, andgenerally higher expression of hsa-let-7g in patients with advanced tumor classification. The results of CCK-8 and apoptosis detectionexperiments showed that the inhibition of hsa-let-7g significantly inhibited proliferation of A549 and H1944 cells, but also promotedapoptosis. HOXB1 is a specific target of hsa-let-7g, and downregulation of HOXB1 in lung cancer cells reversed the suppressiveeffects caused by knocking down hsa-let-7g. Conclusion: These data collectively suggest that the expression of hsa-let-7g inhibits lung cancer cells apoptosis and promotesproliferation by down-regulating HOXB1. The results from this study demonstrate the potential of hsa-let-7g/HOXB1 axis as atherapeutic target for the treatment of lung cancer.
참고문헌 (30)
- Bray F, "Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 68, pp.394~424 (2018)
- Siegel RL, "Cancer statistics, 2019", CA Cancer J Clin, 69, pp.7~34 (2019)
- Woodard GA, "Lung cancer staging and prognosis", Cancer Treat Res, 170, pp.47~75 (2016)
- Nasim F, "Lung cancer", Med Clin North Am, 103, pp.463~473 (2019)
- Cech TR, "The noncoding RNA revolution-trashing old rules to forge new ones", Cell, 157, pp.77~94 (2014)
- Hu X, "A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer", Cancer Cell, 26, pp.344~357 (2014)
- Martens-Uzunova ES, "Long noncoding RNA in prostate, bladder, and kidney cancer", Eur Urol, 65, pp.1140~1151 (2014)
- Del Vescovo V, "microRNA and lung cancer", Adv Exp Med Biol, 889, pp.153~177 (2015)
- Li H, "miR-1254 promotes lung cancer cell proliferation by targeting SFRP1", Biomed Pharmacother, 92, pp.913~918 (2017)
- Dimitrova N, "Stromal expression of miR-143", 145 promotes neoangiogenesis in lung cancer development, 2016, pp.6, 188~201
- Yang Y, "MicroRNA-218functions as a tumor suppressor in lung cancer by targeting IL-6", STAT3 and negatively correlates with poor prognosis, 2017, pp.16, 141~
- Hu H, "Hsa-let-7g miRNA regulates the antitumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes", J Toxicol Sci, 40, pp.329~338 (2015)
- Nakajima G, "Non-coding microRNAs hsa-let-7g and hsa-miR-181b are associated with chemoresponse to S-1 in colon cancer", Cancer Genomics Proteomics, 3, pp.317~324 (2006)
- Hu H, "A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD", Int J Chron Obstruct Pulmon Dis, 10, pp.1641~1649 (2015)
- Han L, "HOXB1 is a tumor suppressor gene regulated by miR-3175 in glioma", PLoS One, 10, pp.e0142387~ (2015)
- Roux M, "Hoxa1 and Hoxb1 are required for pharyngeal arch artery development", Mech Dev, 143, pp.1~8 (2017)
- Morgan R, "Targeting the HOX", PBX dimer in breast cancer, 2012, pp.136, 389~398
- Guazzi S, "Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and the upstream sequence of the Otx2 gene in embryonal carcinoma cells", J Biol Chem, 273, pp.11092~11099 (1998)
- Zhou JL, "Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway", Biomed Pharmacother, 109, pp.2335~2341 (2019)
- Tafrihi M, "MiRNAs : biology, biogenesis, their web-based tools, and databases", Microrna, 8, pp.4~27 (2019)
- Rupaimoole R, "MicroRNA therapeutics : towards a new era for the management of cancer and other diseases", Nat Rev Drug Discov, 16, pp.203~222 (2017)
- Xu G, "miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2", Mol Cell Biochem, 443, pp.151~157 (2018)
- Jiang LP, "Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small-cell lung cancer", Future Oncol, 12, pp.1105~1115 (2016)
- Li J, "miRNA 1284 inhibits cell growth and induces apoptosis of lung cancer cells", Mol Med Rep, 16, pp.3049~3054 (2017)
- Lan FF, "Hsa-let-7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c-Myc and upregulation of p16(INK4A)", Int J Cancer, 128, pp.319~331 (2011)
- Wang L, "MicroRNA let-7g directly targets forkhead Box C2(FOXC2)to modulate bone metastasis in breast cancer", Open Med(Wars), 12, pp.157~162 (2017)
- Salmena L, "A ceRNA hypothesis : the Rosetta Stone of a hidden RNA language", Cell, 146, pp.353~358 (2011)
- Arenkiel BR, "Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry", Genes Dev, 18, pp.1539~1552 (2004)
- Roux M, "Hoxb1regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development", Dev Biol, 406, pp.247~258 (2015)
- López R, "HOXB homeobox gene expression in cervical carcinoma", Int J Gynecol Cancer, 16, pp.329~335 (2006)