LncRNA H19 promotes lung cancer proliferation and metastasis by inhibiting miR-200a function
- 45 Downloads
Lung cancer is the major cause leading to cancer mortality, and the 5-year survival rate for patients with lung cancer still remains low. It is urgent to fully understand the development and progression of lung cancer to discover new therapeutic targets and develop new therapeutic approaches. H19 was documented to be upregulated in lung cancer and related to cell proliferation. However, it is still unclear if H19 has other functions in lung cancer. The mRNA levels of genes were detected by qRT-PCR, and the cell proliferation rate and cell viability were measured through cell count assay and MTT assay. Transwell assays were applied to detect cell abilities to migration and invasion, while luciferase reporter assay and RNA pull-down assay were used to examine interaction between H19 and miR-200a. H19 expression was elevated in the lung cancer tissues and cell lines, while H19 overexpression promoted the lung cancer cell growth, cell migration and invasion, as well as the epithelial mesenchymal transition (EMT). Meantime, RNA pull-down assay showed that H19 interacted with miR-200a, and miR-200a inhibited the activity of H19-fused luciferase. Furthermore, H19 overexpression inhibited miR-200a function and thereby upregulated miR-200a target genes, ZEB1 and ZEB2.H19 sponged and inhibited miR-200a to de-repress expression of ZEB1 and ZEB2, and thereby enhanced lung cancer proliferation and metastasis.
KeywordsH19 miR-200a Lung cancer Proliferation Metastasis
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human and/or animal rights
This study had been approved by The Human Research Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University.
Written consents were derived from the participants.
- 5.Sudo T, Iwaya T, Nishida N, Sawada G, Takahashi Y, Ishibashi M, Shibata K, Fujita H, Shirouzu K, Mori M, Mimori K (2013) Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma. Ann Surg Oncol 20(Suppl 3):S324–335. https://doi.org/10.1245/s10434-012-2418-z CrossRefGoogle Scholar
- 10.Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T, Takahashi T (1995) Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10:1193–1198Google Scholar
- 11.Mizrahi A, Czerniak A, Levy T, Amiur S, Gallula J, Matouk I, Abu-lail R, Sorin V, Birman T, de Groot N, Hochberg A, Ohana P (2009) Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J Transl Med 7:69. https://doi.org/10.1186/1479-5876-7-69 CrossRefGoogle Scholar
- 12.Nakagawa H, Chadwick RB, Peltomaki P, Plass C, Nakamura Y, de La Chapelle A (2001) Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19-associated CTCF-binding sites in colorectal cancer. Proc Natl Acad Sci USA 98:591–596. https://doi.org/10.1073/pnas.011528698 CrossRefGoogle Scholar
- 20.Park IY, Sohn BH, Choo JH, Joe CO, Seong JK, Lee YI, Chung JH (2005) Deregulation of DNA methyltransferases and loss of parental methylation at the insulin-like growth factor II (Igf2)/H19 loci in p53 knockout mice prior to tumor development. J Cell Biochem 94:585–596. https://doi.org/10.1002/jcb.20263 CrossRefGoogle Scholar
- 24.Lehman TA, Bennett WP, Metcalf RA, Welsh JA, Ecker J, Modali RV, Ullrich S, Romano JW, Appella E, Testa JR et al (1991) p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res 51:4090–4096Google Scholar
- 25.Cui J, Mo J, Luo M, Yu Q, Zhou S, Li T, Zhang Y, Luo W (2015) c-Myc-activated long non-coding RNA H19 downregulates miR-107 and promotes cell cycle progression of non-small cell lung cancer. Int J Clin Exp Pathol 8:12400–12409Google Scholar
- 34.Yoneyama K, Ishibashi O, Kawase R, Kurose K, Takeshita T (2015) miR-200a, miR-200b and miR-429 are onco-miRs that target the PTEN gene in endometrioid endometrial carcinoma. Anticancer Res 35:1401–1410Google Scholar