Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

Author(s): Gang Chen and Bo Ye*

Volume 22, Issue 4, 2019

Page: [238 - 244] Pages: 7

DOI: 10.2174/1386207322666190410151945

Price: $65

Abstract

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development.

Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT.

Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells.

Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

Keywords: Non-small cell lung cancer, miRNA, TGF-β, epithelial-to-mesenchymal transition, miRNAs expression, metastasis.

[1]
Ramaswami, R.; Paulino, E.; Barrichello, A.; Nogueira-Rodrigues, A.; Bukowski, A.; St Louis, J.; Goss, P.E. Disparities in breast, lung, and cervical cancer trials worldwide. J. Glob. Oncol., 2018, 4, 1-11.
[2]
Li, Y.; Shang, Y.; Wang, W.; Ning, S.; Chen, H. lung cancer and pulmonary embolism: What is the relationship? J. Cancer, 2018, 9(17), 3046-3057.
[3]
Gupta, G.; Singh, R.; Kotasthane, D.S.; Kotasthane, V.D. Myelodysplastic syndromes/neoplasms: Recent classification system based on World Health Organization Classification of Tumors - International Agency for Research on Cancer for Hematopoietic and Lymphoid Tissues. J. Blood Med., 2010, 1, 171-182.
[4]
Hall, B.R.; Cannon, A.; Atri, P.; Wichman, C.S.; Smith, L.M.; Kumar, S.; Batra, S.K.; Wang, H.; Ganti, A.K.; Sasson, A.R.; Are, C. A comparative analysis of survival and funding discrepancies in cancers with high mortality. Ann. Surg., 2018. [Epub ahead of print].
[http://dx.doi.org/10.1097/SLA.0000000000003042]
[5]
Chen, A.; Liu, S.; Lu, X.; Wei, L.; Chen, Y. Inhibition of microRNA-939 suppresses the development of human non-small cell lung cancer via the upregulation of tissue inhibitor of metalloproteinases 2. Mol. Med. Rep., 2018, 18(6), 4831-4838.
[6]
Park, K.S.; Moon, Y.W.; Raffeld, M.; Lee, D.H.; Wang, Y.; Giaccone, G. High cripto-1 and low miR-205 expression levels as prognostic markers in early stage non-small cell lung cancer. Lung Cancer, 2018, 116, 38-45.
[7]
Yin, Q.; Han, Y.; Zhu, D.; Li, Z.; Shan, S.; Jin, W.; Lu, Q.; Ren, T. miR-145 and miR-497 suppress TGF-β-induced epithelial-mesenchymal transition of non-small cell lung cancer by targeting MTDH. Cancer Cell Int., 2018, 18, 105.
[8]
Nishijima, N.; Seike, M.; Soeno, C.; Chiba, M.; Miyanaga, A.; Noro, R.; Sugano, T.; Matsumoto, M.; Kubota, K.; Gemma, A. miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells. Int. J. Oncol., 2016, 48(3), 937-944.
[9]
Li, X.; Han, J.; Zhu, H.; Peng, L.; Chen, Z. miR-181b-5p mediates TGF-β1-induced epithelial-to-mesenchymal transition in non-small cell lung cancer stem-like cells derived from lung adenocarcinoma A549 cells. Int. J. Oncol., 2017, 51(1), 158-168.
[10]
Liu, X.; Shi, H.; Liu, B.; Li, J.; Liu, Y.; Yu, B. miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer. Acta Biochim. Biophys. Sin. (Shanghai), 2015, 47(6), 431-440.
[11]
Chi, Y.; Jin, Q.; Liu, X.; Xu, L.; He, X.; Shen, Y.; Zhou, Q.; Zhang, J.; Jin, M. miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17. Cancer Sci., 2017, 108(12), 2366-2372.
[12]
Lin, J.; Chen, Y.; Liu, L.; Shen, A.; Zheng, W. MicroRNA-155-5p suppresses the migration and invasion of lung adenocarcinoma A549 cells by targeting Smad2. Oncol. Lett., 2018, 16(2), 2444-2452.
[13]
Qi, L.; Liu, F.; Zhang, F.; Zhang, S.; Lv, L.; Bi, Y.; Yu, Y. lncRNA NEAT1 competes against let-7a to contribute to non-small cell lung cancer proliferation and metastasis. Biomed. Pharmacother., 2018, 103, 1507-1515.
[14]
Li, L.; Sun, Y.; Feng, M.; Wang, L.; Liu, J. Clinical significance of blood-based miRNAs as biomarkers of non-small cell lung cancer. Oncol. Lett., 2018, 15(6), 8915-8925.
[15]
He, P.; Qiu, K.; Jia, Y. Modeling of mesenchymal hybrid epithelial state and phenotypic transitions in EMT and MET processes of cancer cells. Sci. Rep., 2018, 8(1), 14323.
[16]
Gao, D.; Wang, L.; Zhang, H.; Yan, X.; Yang, J.; Zhou, R.; Chang, X.; Sun, Y.; Tian, S.; Yao, Z.; Zhang, K.; Liu, Z.; Ma, Z. Spleen tyrosine kinase SYK(L) interacts with YY1 and coordinately suppresses SNAI2 transcription in lung cancer cells. FEBS J., 2018, 285(22), 4229-4245.
[17]
Lei, H.; Gao, Y.; Xu, X. LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145. Acta Biochim. Biophys. Sin. (Shanghai), 2017, 49(7), 588-597.
[18]
Maeda, S.; Nakagawa, H. Roles of E-cadherin in Hepatocarcinogenesis. Innovative Medicine: Basic Research and Development; Springer: Tokyo, Japan, 2015.
[19]
Stoops, S.L.; Pearson, A.S.; Weaver, C.; Waterson, A.G.; Days, E.; Farmer, C.; Brady, S.; Weaver, C.D.; Beauchamp, R.D.; Lindsley, C.W. Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells. ACS Chem. Biol., 2011, 6(5), 452-465.
[20]
Zhao, X.; Yang, H.; Chen, M.; Song, X.; Yu, C.; Zhao, Y.; Wu, Y. Reference gene selection for quantitative real-time PCR of mycelia from lentinula edodes under high-temperature stress. BioMed Res. Int., 2018, 20181670328
[21]
Wang, Y.C.; Yang, X.; Wei, W.B.; Xu, X.L. Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein. Int. J. Ophthalmol., 2018, 11(8), 1258-1268.
[22]
Zhang, Y.; Huang, P.; Liu, X.; Xiang, Y.; Zhang, T.; Wu, Y.; Xu, J.; Sun, Z.; Zhen, W.; Zhang, L.; Si, Y.; Liu, Y. Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis. J. Pharmacol. Sci., 2018, 137(3), 305-312.
[23]
Chen, B.; Tan, Z.; Gao, J.; Wu, W.; Liu, L.; Jin, W.; Cao, Y.; Zhao, S.; Zhang, W.; Qiu, Z.; Liu, D.; Mo, X.; Li, W.J. Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer. J. Exp. Clin. Cancer Res., 2015, 34, 126.
[24]
Ryu, J.S.; Ryu, H.J.; Lee, S.N.; Memon, A.; Lee, S.K.; Nam, H.S.; Kim, H.J.; Lee, K.H.; Cho, J.H.; Hwang, S.S. Prognostic impact of minimal pleural effusion in non-small-cell lung cancer. J. Clin. Oncol., 2014, 32(9), 960-967.
[25]
25. Zhang, L.G.; Zhou, X.K.; Zhou, R.J.; Lv, H.Z.; Li, W.P. Long non-coding RNA LINC00673 promotes hepatocellular carcinoma progression and metastasis through negatively regulating miR-205. Am. J. Cancer Res., 2017, 7(12), 2536-2544.
[26]
26. Duan, X.; Fu, Z.; Gao, L.; Zhou, J.; Deng, X.; Luo, X.; Fang, W.; Luo, R. Direct interaction between miR-203 and ZEB2 suppresses epithelial-mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance. Acta Biochim. Biophys. Sin. (Shanghai), 2016, 48(11), 1042-1049.
[27]
27. Shu, C.; Yan, D.; Mo, Y.; Gu, J.; Shah, N.; He, J. Long noncoding RNA lncARSR promotes epithelial ovarian cancer cell proliferation and invasion by association with HuR and miR-200 family. Am. J. Cancer Res., 2018, 8(6), 981-992.
[28]
28. Han, J.; Wang, F.; Lan, Y.; Wang, J.; Nie, C.; Liang, Y.; Song, R.; Zheng, T.; Pan, S.; Pei, T.; Xie, C.; Yang, G.; Liu, X.; Zhu, M. KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling. Oncogene, 2019, 38(3), 406-420.
[29]
29. Cardiff, R.D. Epithelial to Mesenchymal Transition Tumors: Fallacious or Snail’s Pace? Clin. Cancer Res., 2005, 11, 8534-8537.
[30]
30. Thompson, E.W.; Newgreen, D.F.; Tarin. D. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res., 2005, 65, 5991-5995. , discussion 5995.
[31]
31. Lobb, R.J.; Amerongen, R. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance. Int. J. Cancer, 2017, 141(3), 614-620.
[32]
32. Fang, H.; Liu, H.M.; Wu, W.H.; Liu, H.; Pan, Y.; Li, W.J. Upregulation of long noncoding RNA CCAT1-L promotes epithelial-mesenchymal transition in gastric adenocarcinoma. OncoTargets Ther., 2018, 1, 5647-5655.
[33]
33. Sun, Y.; Jiang, X.; Lu, Y.; Zhu, J.; Yu, L.; Ma, B.; Zhang, Q. Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma. Chem. Biol. Interact., 2018, 296, 57-64.
[34]
34. Lee, S.Y.; Na, Y.J.; Jeong, Y.A.; Kim, J.L.; Oh, S.C.; Lee, D.H. Upregulation of EphB3 in gastric cancer with acquired resistance to a FGFR inhibitor. Int. J. Biochem. Cell Biol., 2018, 102, 128-137.
[35]
35. Chang, S.N.; Lee, J.M.; Oh, H.; Kim, U.; Ryu, B.; Park, J.H. Troglitazone inhibits the migration and invasion of PC-3 human prostate cancer cells by upregulating E-cadherin and glutathione peroxidase 3. Oncol. Lett., 2018, 16(4), 5482-5488.
[36]
36. Song, G.; Banov, D.; Bassani, A.S.; Valdez, B.C. Evaluation of the safety, cell migration, and mucoadhesive properties of a mucoadhesive polymer blend in human oral mucosa. AAPS PharmSciTech, 2017, 18(5), 1617-1623.
[37]
37. Zhao, Y.F.; Qiao, S.P.; Shi, S.L.; Yao, L.F.; Hou, X.L.; Li, C.F.; Lin, F.H.; Guo, K.; Acharya, A.; Chen, X.B.; Nie, Y.; Tian, W.M. Modulating three-dimensional microenvironment with hyaluronan of different molecular weights alters breast cancer cell invasion behavior. ACS Appl. Mater. Interfaces, 2017, 9(11), 9327-9338.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy