Long non‑coding RNA HOX transcript antisense RNA promotes expression of 14‑3‑3σ in non‑small cell lung cancer

Wang,Ranran; Yan,Bin; Li,Zheng; Jiang,Yiqun; Mao,Chao; Wang,Xiang; Zhou,Xinmin

doi:10.3892/etm.2017.5041

Long non‑coding RNA HOX transcript antisense RNA promotes expression of 14‑3‑3σ in non‑small cell lung cancer

Authors:
- Ranran Wang
- Bin Yan
- Zheng Li
- Yiqun Jiang
- Chao Mao
- Xiang Wang
- Xinmin Zhou
View Affiliations

Affiliations: Department of Thoracic and Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Cancer Research Institute, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: August 28, 2017 https://doi.org/10.3892/etm.2017.5041
Pages: 4503-4508

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Evidence suggests that both 14‑3‑3σ and long non‑coding RNA HOX transcript antisense RNA (HOTAIR) are involved in the tumorigenesis and progression of lung cancer. In the present study, the potential association between 14‑3‑3σ and HOTAIR in non‑small cell lung cancer (NSCLC) was investigated. In tissue samples collected from 54 patients with NSCLC, expression of HOTAIR and 14‑3‑3σ was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). After stable ectopic expression of HOTAIR and stable HOTAIR knockdown in PC9 cancer cells, the effect of HOTAIR on levels of mRNA and protein 14‑3‑3σ expression levels were detected using RT‑qPCR and western blotting, respectively. Expression of HOTAIR and 14‑3‑3σ in NSCLC tissues was significantly higher than in adjacent non‑cancerous lung tissue (P<0.05). Correlation analysis also identified a correlation between levels of HOTAIR and 14‑3‑3σ expression in NSCLC tissues (r=0.725, P=0.0005). In addition, overexpression and knockdown of HOTAIR in the human NSCLC cell line PC9 led to the upregulation and downregulation of 14‑3‑3σ, respectively, at both the mRNA and protein levels (all P<0.05). To the best of our knowledge, the present study provides the first in vivo and in vitro evidence to suggest that HOTAIR promotes the expression of 14‑3‑3σ in NSCLC. The potential association between HOTAIR and 14‑3‑3σ indicates that both biomolecules may be viable targets in anticancer therapy.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Chang A: Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer. 71:3–10. 2011. View Article : Google Scholar : PubMed/NCBI
3	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI
4	Raungrut P, Wongkotsila A, Lirdprapamongkol K, Svasti J, Geater SL, Phukaoloun M, Suwiwat S and Thongsuksai P: Prognostic significance of 14-3-3γ overexpression in advanced non-small cell lung cancer. Asian Pac J Cancer Prev. 15:3513–3518. 2014. View Article : Google Scholar : PubMed/NCBI
5	Porter GW, Khuri FR and Fu H: Dynamic 14-3-3/client protein interactions integrate survival and apoptotic pathways. Sem Cancer Biol. 16:193–202. 2006. View Article : Google Scholar
6	Morrison D: The 14-3-3 proteins: Integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol. 19:16–23. 2008. View Article : Google Scholar : PubMed/NCBI
7	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
8	Okada T, Masuda N, Fukai Y, Shimura T, Nishida Y, Hosouchi Y, Kashiwabara K, Nakajima T and Kuwano H: Immunohistochemical expression of 14-3-3 sigma protein in intraductal papillary-mucinous tumor and invasive ductal carcinoma of the pancreas. Anticancer Res. 26:3105–3110. 2006.PubMed/NCBI
9	Shiba-Ishii A, Kano J, Morishita Y, Sato Y, Minami Y and Noguchi M: High expression of stratifin is a universal abnormality during the course of malignant progression of early-stage lung adenocarcinoma. Int J Cancer. 129:2445–2453. 2011. View Article : Google Scholar : PubMed/NCBI
10	Boudreau A, Tanner K, Wang D, Geyer FC, Reis-Filho JS and Bissell MJ: 14-3-3σ stabilizes a complex of soluble actin and intermediate filament to enable breast tumor invasion. Proc Natl Acad Sci USA. 110:E3937–E3944. 2013. View Article : Google Scholar : PubMed/NCBI
11	Neal CL and Yu D: 14-3-3ζ as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets. 14:1343–1354. 2010. View Article : Google Scholar : PubMed/NCBI
12	Qi W, Liu X, Qiao D and Martinez JD: Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues. Int J Cancer. 113:359–363. 2005. View Article : Google Scholar : PubMed/NCBI
13	Radhakrishnan VM, Jensen TJ, Cui H, Futscher BW and Martinez JD: Hypomethylation of the 14-3-3σ promoter leads to increased expression in non-small cell lung cancer. Genes Chromosomes Cancer. 50:830–836. 2011. View Article : Google Scholar : PubMed/NCBI
14	Cetintas VB, Tetik A, Cok G, Kucukaslan AS, Kosova B, Gunduz C, Veral A and Eroglu Z: Role of 14-3-3σ in resistance to cisplatin in non-small cell lung cancer cells. Cell Biol Int. 37:78–86. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhao W, An Y, Liang Y and Xie XW: Role of HOTAIR long noncoding RNA in metastatic progression of lung cancer. Eur Rev Med Pharmacol Sci. 18:1930–1936. 2014.PubMed/NCBI
16	Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
17	Liu XH, Liu ZL, Sun M, Liu J, Wang ZX and De W: The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer. 13:4642013. View Article : Google Scholar : PubMed/NCBI
18	Greene FL and Sobin LH: The staging of cancer: A retrospective and prospective appraisal. CA Cancer J Clin. 58:180–190. 2008. View Article : Google Scholar : PubMed/NCBI
19	Gospodarowicz MK, Miller D, Groome PA, Greene FL, Logan PA and Sobin LH: The process for continuous improvement of the TNM classification. Cancer. 100:1–5. 2004. View Article : Google Scholar : PubMed/NCBI
20	Wang R, Shi Y, Chen L, Jiang Y, Mao C, Yan B, Liu S, Shan B, Tao Y and Wang X: The ratio of FoxA1 to FoxA2 in lung adenocarcinoma is regulated by LncRNA HOTAIR andchromatin remodeling factor LSH. Sci Rep. 5:178262015. View Article : Google Scholar : PubMed/NCBI
21	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
22	Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK and Shan B: Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol. 6:352013. View Article : Google Scholar : PubMed/NCBI
23	Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E and Chang HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 129:1311–1323. 2007. View Article : Google Scholar : PubMed/NCBI
24	Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S and Safe S: HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 32:1616–1625. 2013. View Article : Google Scholar : PubMed/NCBI
25	Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, et al: Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res. 72:1126–1136. 2012. View Article : Google Scholar : PubMed/NCBI