Original Article

LncRNA HOTAIR Promotes Proliferation of Malignant Melanoma Cells Through NF-κB Pathway


Background: To study the effects of long non-coding ribonucleic acid (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) on the proliferation and apoptosis of malignant melanoma cells, and to explore its specific regulatory mechanism through the nuclear factor-κB (NF-κB) signaling pathway.

Methods: LncRNA HOTAIR small-interfering RNAs (siRNAs) were designed and synthesized, and the effects of si-HOTAIR transfection on the proliferation and apoptosis of malignant melanoma cells were detected via cell counting kit-8 (CCK-8) assay, 4',6-diamidino-2-phenylindole (DAPI) staining assay and flow cytometry, respectively. The gene expressions were determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the changes in NF-κB pathway-related proteins and apoptosis-associated proteins after interference in lncRNA HOTAIR were detected via Western blotting, and the level of NF-κB in each group was determined via ELISA.

Results: The results of CCK-8 assay revealed that the cell proliferation rate significantly declined gradually in si-HOTAIR group compared with that in si-NC group and control group (P<0.05). The results of Western blotting and ELISA showed that the activity of NF-κB in si-HOTAIR group was weakened (P<0.05), suggesting that down-regulation of HOTAIR can suppress the activity of NF-κB. Compared with si-NC group and control group, si-HOTAIR group had remarkably increased gene and protein expressions of pro-apoptotic Bax, and remarkably decreased gene and protein expressions of anti-apoptotic Bcl-2 (P<0.05), demonstrating that down-regulation of HOTAIR can promote apoptosis.

Conclusion: Down-regulation of lncRNA HOTAIR can inhibit the proliferation and promote the apoptosis of malignant melanoma cells and suppress the NF-κB pathway.

1. Luo C, Shen J (2017). Research progress in advanced melanoma. Cancer Lett, 397: 120-126.
2. Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF (2005). Meta-analysis of risk factors for cutane-ous melanoma: II. Sun exposure. Eur J Cancer, 41: 45-60.
3. Reed KB, Brewer JD, Lohse CM, Bringe KE, Pruitt CN, Gibson LE (2012). In-creasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin Proc, 87: 328-334.
4. Miller KD, Siegel RL, Lin CC, et al (2016). Cancer treatment and survivorship statis-tics, 2016. CA Cancer J Clin, 66: 271-289.
5. Mercer TR, Dinger ME, Mattick JS (2009). Long non-coding RNAs: insights into functions. Nat Rev Genet, 10: 155-159.
6. Yao Y, Li J, Wang L (2014). Large interven-ing non-coding RNA HOTAIR is an in-dicator of poor prognosis and a thera-peutic target in human cancers. Int J Mol Sci, 15: 18985-18999.
7. Zhang J, Liu X, You LH, Zhou RZ (2016). Significant association between long non-coding RNA HOTAIR polymorphisms and cancer susceptibility: a meta-analysis. Onco Targets Ther, 9: 3335-3343.
8. Carrion K, Dyo J, Patel V, Sasik R, Mo-hamed SA, Hardiman G, Nigam V (2014). The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of cal-cification genes. PLoS One, 9: e96577.
9. Song J, Kim D, Han J, Kim Y, Lee M, Jin EJ (2015). PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med, 15: 121-126.
10. Mao X, Su Z, Mookhtiar AK (2017). Long non-coding RNA: a versatile regulator of the nuclear factor-kappaB signalling cir-cuit. Immunology, 150: 379-388.
11. Gupta RA, Shah N, Wang KC, et al (2010). Long non-coding RNA HOTAIR repro-grams chromatin state to promote cancer metastasis. Nature, 464: 1071-1076.
12. Wang X, Liu W, Wang P, Li S (2018). RNA interference of long noncoding RNA HOTAIR suppresses autophagy and promotes apoptosis and sensitivity to cisplatin in oral squamous cell carcinoma. J Oral Pathol Med, 47: 930-937.
13. Kogo R, Shimamura T, Mimori K, et al (2011). Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res, 71: 6320-6326.
14. Li J, Wang J, Zhong Y, Guo R, Chu D, Qiu H, Yuan Z (2017). HOTAIR: a key regu-lator in gynecologic cancers. Cancer Cell Int, 17: 65.
15. Cantile M, Cindolo L, Napodano G, Altieri V, Cillo C (2003). Hyperexpression of lo-cus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas. Onco-gene, 22: 6462-6468.
16. Cantile M, Scognamiglio G, Anniciello A, et al (2012). Increased HOX C13 expres-sion in metastatic melanoma progression. J Transl Med, 10: 91.
17. Panday A, Inda ME, Bagam P, Sahoo MK, Osorio D, Batra S (2016). Transcription Factor NF-kappaB: An Update on Inter-vention Strategies. Arch Immunol Ther Exp (Warsz), 64: 463-483.
18. Mobley AK, Braeuer RR, Kamiya T, Sho-shan E, Bar-Eli M (2012). Driving tran-scriptional regulators in melanoma metas-tasis. Cancer Metastasis Rev, 31: 621-632.
19. Liu QH, Ma LS (2018). Knockdown of thrombospondin 2 inhibits metastasis through modulation of PI3K signaling pathway in uveal melanoma cell line M23. Eur Rev Med Pharmacol Sci, 22: 6230-6238.
20. Chen WK, Yu XH, Yang W, Wang C, He WS, Yan YG, Zhang J, Wang WJ (2017). lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis. Cell Prolif, 50: e12313.
21. Yang L, Zhang X, Li H, Liu J (2016). The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Mol Biosyst, 12: 2605-2612.
22. Wu Y, Zhang L, Zhang L, et al (2015). Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by re-cruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J On-col, 46: 2586-2594.
23. Luan W, Li R, Liu L, et al (2017). Long non-coding RNA HOTAIR acts as a compet-ing endogenous RNA to promote malig-nant melanoma progression by sponging miR-152-3p. Oncotarget, 8: 85401-85414.
24. Barham W, Chen L, Tikhomirov O, Onish-ko H, Gleaves L, Stricker TP, Blackwell TS, Yull FE (2015). Aberrant activation of NF-kappaB signaling in mammary epi-thelium leads to abnormal growth and ductal carcinoma in situ. BMC Cancer, 15: 647.
25. Weng H, Deng Y, Xie Y, Liu H, Gong F (2013). Expression and significance of HMGB1, TLR4 and NF-kappaB p65 in human epidermal tumors. BMC Cancer, 13: 311.
IssueVol 49 No 10 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i10.4696
lncRNA HOTAIR Malignant melanoma cells NF-κB pathway

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
WANG J, CHEN J, JING G, DONG D. LncRNA HOTAIR Promotes Proliferation of Malignant Melanoma Cells Through NF-κB Pathway. Iran J Public Health. 2020;49(10):1931-1939.