Cortex Mori extract inhibits migration and invasion of lung adenocarcinoma cells by blocking RECQL4-induced NF-κB and ERK signaling pathways
Main Article Content
Keywords
Cortex Mori (CM) extract, RECQL4, lung adenocarcinoma, NF-κB and ERK signaling pathways
Abstract
Lung adenocarcinoma (LUAC) is one of the usual tumors of the lung with high mortality rate. RecQ-like helicase 4 (RECQL4) gene has been discovered to take part in the progression of different cancers by undertaking as an oncogene, and is relevant with poor prognosis of LUAC. Cortex Mori (CM) extract has been investigated to affect cellular progress to regulate different diseases. However, the detailed functioning of RECQL4 and CM extract, as well as their regulatory mechanisms in LUAC, has not been illustrated. The purpose of the present study was to probe the impact of RECQL4 and CM extract on progression of LUAC. The expression of RECQL4 in LUAC was assessed by The Cancer Genome Atlas (TCGA) database. The mRNA expression of RECQL4 was examined by real-time quantitative polymerase chain reaction. The protein expressions (epithelial–mesenchymal transition [EMT] process, nuclear factor kappa B [NF-κB] and extracellular signal-regulated kinase [ERK] signaling pathways-related proteins) were determined by Western blot analysis. The cell proliferation was tested through cell counting kit-8 assay. Cell migration and invasion was affirmed by wound-healing and transwell assays. The cell senescence was assessed through senescence-associated beta-galactosidase staining. The cell cycle was inspected by flow cytometry. Our findings demonstrated that RECQL4 exhibited higher expression in LUAC tissues and cell lines. Through functional experiments, we found that RECQL4 facilitated cell proliferation, migration, and invasion as well as EMT progression. In addition, RECQL4 relieved cell cycle arrest and cell senescence. Moreover, RECQL4 activated NF-κB and ERK signaling pathways by enhancing phospho(p)-p65–p65 and p-ERK–ERK levels in LUAC. CM extract exhibited antitumor effects in LUAC, and blocked RECQL4-induced NF-κB and ERK signaling pathways. Our results manifested that CM extract inhibited migration and invasion of LUAC cells by blocking RECQL4-induced NF-κB and ERK signaling pathways. This result could provide a promising therapeutic strategy for LUAC.
Downloads
References
Bischoff, J., 2019. Endothelial-to-mesenchymal transition. Circulation Research 124(8): 1163–1165. 10.1161/CIRCRESAHA.119.314813
Chaffer, C.L. and Weinberg, R.A., 2011. A perspective on cancer cell metastasis. Science 331(6024): 1559–1564. 10.1126/science.1203543
Croteau D.L., Singh D.K., Hoh Ferrarelli L., Lu H., Bohr V.A. RECQL4 in genomic instability and aging. Trends in Genetics 28(12): 624–631. 10.1016/j.tig.2012.08.003
Denisenko, T.V., Budkevich, I.N. and Zhivotovsky, B., 2018. Cell death-based treatment of lung adenocarcinoma. Cell Death and Disease 9(2): 117. 10.1038/s41419-017-0063-y
Du, B. and Shim, J.S., 2016. Targeting epithelial-mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules 21(7): 965. 10.3390/molecules21070965
Fong Y.C., Liu S.C., Huang C.Y., Li T.M., Hsu S.F., Kao S.T., et al. 2009. Osteopontin increases lung cancer cells migration via activation of the alphavbeta3 integrin/FAK/Akt and NF-kappaB-dependent pathway. Lung Cancer 64(3): 263–270. 10.1016/j.lungcan.2008.09.003
Guo L., Li Y., Zhao C., Peng J., Song K., Chen L., et al. 2020. RECQL4, negatively regulated by miR-10a-5p, facilitates cell proliferation and invasion via MAFB in ovarian cancer. Frontiers in Oncology 10: 524128. 10.3389/fonc.2020.524128
Herbst, R.S., Morgensztern, D. and Boshoff, C., 2018. The biology and management of non-small cell lung cancer. Nature 553(7689): 446–454. 10.1038/nature25183
Hirsch F.R., Scagliotti G.V., Mulshine J.L., Kwon R., Curran W.J., Jr., Wu Y.L., et al. 2017. Lung cancer: current therapies and new targeted treatments. Lancet 389(10066): 299–311. 10.1016/S0140-6736(16)30958-8
Hu X., Zhang K., Pan G., Wang Y., Shen Y., Peng C., et al. 2022. Cortex mori extracts induce apoptosis and inhibit tumor invasion via blockage of the PI3K/AKT signaling in melanoma cells. Frontiers in Pharmacology 13: 1007279. 10.3389/fphar.2022.1007279
Jiang W., Xu J., Liao Z., Li G., Zhang C., Feng Y. 2021. Prognostic signature for lung adenocarcinoma patients based on cell-cycle-related genes. Frontiers in Cell and Developmental Biology 9: 655950. 10.3389/fcell.2021.655950
Jones, G.S. and Baldwin, D.R., 2018. Recent advances in the management of lung cancer. Clinical Medicine (London) 18(Suppl 2): s41–s46. 10.7861/clinmedicine.18-2-s41
Kitao S., Lindor N.M., Shiratori M., Furuichi Y., Shimamoto A., 1999. Rothmund–Thomson syndrome responsible gene, RECQL4: genomic structure and products. Genomics 61(3): 268–276. 10.1006/geno.1999.5959
Lemjabbar-Alaoui H., Hassan O.U., Yang Y.W., Buchanan P., 2015. Lung cancer: biology and treatment options. Biochimica et Biophysica Acta 1856(2): 189–210. 10.1016/j.bbcan.2015.08.002
Li, Jin., Liao, Dang., Chen, Wu, Liao., 2018a. Upregulation of RECQL4 expression predicts poor prognosis in hepatocellular carcinoma. Oncology Letters 15(4): 4248–4254. 10.3892/ol.2018.7860
Li X., Bao C., Ma Z., Xu B., Ying X., Liu X., et al. 2018b. Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway. Toxicology Letters 294: 44–50. 10.1016/j.toxlet.2018.05.009
Liu X., Zhao W., Wang W., Lin S., Yang L., 2017. Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-κB and Erk pathway. Biomedicine & Pharmacotherapy 92: 429–436. 10.1016/j.biopha.2017.05.102
Lyu G., Su P., Hao X., Chen S., Ren S., Zhao Z., et al. 2021. RECQL4 regulates DNA damage response and redox homeostasis in esophageal cancer. Cancer Biology & Medicine 18(1): 120–138. 10.20892/j.issn.2095-3941.2020.0105
Ma L.L., Yuan Y.Y., Zhao M., Zhou X.R., Jehangir T., Wang F.Y., et al. 2018. Mori cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats. Chinese Journal of Natural Medicine 16(6): 411–417. 10.1016/S1875-5364(18)30074-8
Mo D., Fang H., Niu K., Liu J., Wu M., Li S., et al. 2016. Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway. Cancer Research 76(10): 3057–3066. 10.1158/0008-5472.CAN-15-2361
Nam S.Y., Yi H.K., Lee J.C., Kim J.C., Song C.H., Park J.W., et al. 2002. Cortex mori extract induces cancer cell apoptosis through inhibition of microtubule assembly. Archives of Pharmacal Research 25(2): 191–196. 10.1007/BF02976562
Nasim F., Sabath B.F., Eapen G.A., 2019. Lung cancer. Medical Clinics of North America 103(3): 463–473. 10.1016/j.mcna.2018.12.006
Nieto, M.A., 2013. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 342(6159): 1234850. 10.1126/science.1234850
Pastushenko, I. and Blanpain, C., 2019. EMT transition states during tumor progression and metastasis. Trends in Cellular Biology 29(3): 212–226. 10.1016/j.tcb.2018.12.001
Piera-Velazquez, S. and Jimenez, S.A., 2019. Endothelial to mesenchymal transition: role in physiology and in the pathogenesis of human diseases. Physiological Reviews 99(2): 1281–1324. 10.1152/physrev.00021.2018
Romaszko, A.M. and Doboszyńska, A., 2018. Multiple primary lung cancer: a literature review. Advances in Clinical and Experimental Medicine 27(5): 725–730. 10.17219/acem/68631
Siitonen H.A., Kopra O., Kääriäinen H., Haravuori H., Winter R.M., Säämänen A.M., Peltonen L., et al. 2003. Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Human Molecular Genetics 12(21): 2837–2844. 10.1093/hmg/ddg306
Su Y., Meador J.A., Calaf G.M., Proietti De-Santis L., Zhao Y., Bohr V.A., et al. 2010. Human RecQL4 helicase plays critical roles in prostate carcinogenesis. Cancer Research 70(22): 9207–9217. 10.1158/0008-5472.CAN-10-1743
Succony L., Rassl D.M., Barker A.P., McCaughan F.M., Rintoul R.C., 2021. Adenocarcinoma spectrum lesions of the lung: detection, pathology and treatment strategies. Cancer Treatment Reviews 99: 102237. 10.1016/j.ctrv.2021.102237
Suhail Y., Cain M.P., Vanaja K., Kurywchak P.A., Levchenko A., Kalluri R., et al. 2019. Systems biology of cancer metastasis. Cell Systems 9(2): 109–127. 10.1016/j.cels.2019.07.003
Thiery J.P., Acloque H., Huang R.Y., Nieto M.A., 2009. Epithelial-mesenchymal transitions in development and disease. Cell 139(5): 871–890. 10.1016/j.cell.2009.11.007
Van Maldergem L., Siitonen H.A., Jalkh N., Chouery E., De Roy M., Delague V., et al. 2006. Revisiting the craniosynostosis-radial ray hypoplasia association: Baller–Gerold syndrome caused by mutations in the RECQL4 gene. Journal of Medical Genetics 43(2): 148–152. 10.1136/jmg.2005.031781
Wang J., Weng Y., Zhang M., Li Y., Fan M., Guo Y., et al. 2016. BMP9 inhibits the growth and migration of lung adenocarcinoma A549 cells in a bone marrow stromal cell-derived microenvironment through the MAPK/ERK and NF-κB pathways. Oncology Reports 36(1): 410–418. 10.3892/or.2016.4796
Wu, F., Wang, L. and Zhou, C., 2021. Lung cancer in China: current and prospect. Current Opinion in Oncology 33(1): 40–46. 10.1097/CCO.0000000000000703
Zhang, Y. and Weinberg, R.A., 2018. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Frontiers in Medicine 12(4): 361–373. 10.1007/s11684-018-0656-6
Zhou F., Wang L., Jin K., Wu Y., 2021. RecQ-like helicase 4 (RECQL4) exacerbates resistance to oxaliplatin in colon adenocarcinoma via activation of the PI3K/AKT signaling pathway. Bioengineered 12(1): 5859–5869. 10.1080/21655979.2021.1964156
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.