Downregulation of lncRNA H19 inhibits the migration and invasion of melanoma cells by inactivating the NF‑κB and PI3K/Akt signaling pathways

Liao,Zhichao; Zhao,Jun; Yang,Yun

doi:10.3892/mmr.2018.8782

Downregulation of lncRNA H19 inhibits the migration and invasion of melanoma cells by inactivating the NF‑κB and PI3K/Akt signaling pathways

Authors:
- Zhichao Liao
- Jun Zhao
- Yun Yang
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Affiliations: Department of Bone and Soft Tissue Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, P.R. China
Published online on: March 20, 2018 https://doi.org/10.3892/mmr.2018.8782
Pages: 7313-7318

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Abstract

As the most aggressive type of skin cancer, melanoma seriously affects human health. Long noncoding (lncRNA) 19 has been demonstrated to be involved in the progression of a number of different types of human cancers. However, the involvement of lncRNA H19 in melanoma remains unknown. Therefore, the present study was performed to investigate the roles of H19 in the development and progression of melanoma. In the present study, 49 patients with melanoma were included. Expression of lncRNA H19 in tumor tissue, adjacent healthy tissue and various cell lines with different treatments was measured by reverse transcription‑quantitative polymerase chain reaction. The effects of H19 knockdown on melanoma cell proliferation, migration and invasion were detected by cell counting kit‑8, wound‑healing and transwell invasion assays, respectively. In addition, the effects of H19 knockdown on the expression of nuclear factor (NF)‑κB pathway‑associated proteins were investigated by western blotting. The results revealed that the expression level of H19 was significantly higher in tumor tissue than in the adjacent healthy tissue of 47 out of 49 patients. H19 knockdown significantly reduced the proliferation, migration and invasion ability of melanoma cells. H19 knockdown also inactivated the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway, which in turn inhibited the activation of the NF‑κB signaling pathway. Thus, downregulation of lncRNA H19 may inhibit the migration and invasion of melanoma cells by inactivating the NF‑κB signaling pathway via the inactivation of the PI3K/Akt signaling pathway. The present study provided references for future studies on the pathogenesis of melanoma and the clinical treatment of this disease.

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1	Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, et al: A landscape of driver mutations in melanoma. Cell. 150:251–263. 2012. View Article : Google Scholar : PubMed/NCBI
2	Allen DC: Malignant melanomaHistopathology Reporting. Springer; London: pp. 207–216. 2013, View Article : Google Scholar
3	Stewart BW and Wild CP: World Cancer Report 2014. IARC Publications; Lyon: 2017
4	Azoury SC and Lange JR: Epidemiology, risk factors, prevention, and early detection of melanoma. Surg Clin North Am. 94(945–62): vii2014. View Article : Google Scholar
5	Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, et al: Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 32:1020–1030. 2014. View Article : Google Scholar : PubMed/NCBI
6	Atefi M, Avramis E, Lassen A, Wong DJ, Robert L, Foulad D, Cerniglia M, Titz B, Chodon T, Graeber TG, et al: Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res. 20:3446–3457. 2014. View Article : Google Scholar : PubMed/NCBI
7	Pal HC, Sharma S, Strickland LR, Katiyar SK, Ballestas ME, Athar M, Elmets CA and Afaq F: Fisetin inhibits human melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways. PLoS One. 9:e863382014. View Article : Google Scholar : PubMed/NCBI
8	Perkel JM: Visiting ‘noncodarnia’. Biotechniques. 54(301): 303–304. 2013.
9	Ning S, Zhang J, Wang P, Zhi H, Wang J, Liu Y, Gao Y, Guo M, Yue M, Wang L and Li X: Lnc2Cancer: A manually curated database of experimentally supported lncRNAs associated with various human cancers. Nucleic Acids Res. 44:D980–D985. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J and Fang G: Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 279:3159–3165. 2012. View Article : Google Scholar : PubMed/NCBI
11	Luo M, Li Z, Wang W, Zeng Y, Liu Z and Qiu J: Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett. 333:213–221. 2013. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS and Perera RJ: The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 71:3852–3862. 2011. View Article : Google Scholar : PubMed/NCBI
14	Tian Y, Zhang X, Hao Y, Fang Z and He Y: Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res. 24:335–341. 2014. View Article : Google Scholar : PubMed/NCBI
15	Tang L, Zhang W, Su B and Yu B: Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma. Biomed Res Int. 2013:2510982013. View Article : Google Scholar : PubMed/NCBI
16	Chen L, Yang H, Xiao Y, Tang X, Li Y, Han Q, Fu J, Yang Y and Zhu Y: LncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivo. Onco Targets Ther. 9:4075–4087. 2016. View Article : Google Scholar : PubMed/NCBI
17	Li H, Yu B, Li J, Su L, Yan M, Zhu Z and Liu B: Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget. 5:2318–2329. 2014. View Article : Google Scholar : PubMed/NCBI
18	Liang WC, Fu WM, Wong CW, Wang Y, Wang WM, Hu GX, Zhang L, Xiao LJ, Wan DC, Zhang JF and Waye MM: The lncRNA H19 promotes epithelial to mesenchymal transition by functioning as miRNA sponges in colorectal cancer. Oncotarget. 6:22513–22525. 2015. View Article : Google Scholar : PubMed/NCBI
19	Zhu M, Chen Q, Liu X, Sun Q, Zhao X, Deng R, Wang Y, Huang J, Xu M, Yan J and Yu J: lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI. FEBS J. 281:3766–3775. 2014. View Article : Google Scholar : PubMed/NCBI
20	Zhou X, Ye F, Yin C, Zhuang Y, Yue G and Zhang G: The interaction between MiR-141 and lncRNA-H19 in regulating cell proliferation and migration in gastric cancer. Cell Physiol Biochem. 36:1440–1452. 2015. View Article : Google Scholar : PubMed/NCBI
21	Shi Y, Wang Y, Luan W, Wang P, Tao T, Zhang J, Qian J, Liu N and You Y: Long non-coding RNA H19 promotes glioma cell invasion by deriving miR-675. PLoS One. 9:e862952014. View Article : Google Scholar : PubMed/NCBI
22	Wang WT, Ye H, Wei PP, Han BW, He B, Chen ZH and Chen YQ: LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner. J Hematol Oncol. 9:1172016. View Article : Google Scholar : PubMed/NCBI
23	Hoesel B and Schmid JA: The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 12:862013. View Article : Google Scholar : PubMed/NCBI
24	Pan JX: LncRNA H19 promotes atherosclerosis by regulating MAPK and NF-kB signaling pathway. Eur Rev Med Pharmacol Sci. 21:322–328. 2017.PubMed/NCBI
25	Hyam SR, Lee IA, Gu W, Kim KA, Jeong JJ, Jang SE, Han MJ and Kim DH: Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages. Eur J Pharmacol. 708:21–29. 2013. View Article : Google Scholar : PubMed/NCBI
26	Han W, Xiong Y, Li Y, Fang W, Ma Y, Liu L, Li F and Zhu X: Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway and TNF-α associated with collagen-induced arthritis. Pharm Biol. 51:13–22. 2013. View Article : Google Scholar : PubMed/NCBI