Prognostic significance of nuclear RNA export factor 3 in hepatocellular carcinoma

Jiang,Jia‑Hao; Gao,Qiang; Ke,Ai‑Wu; Yu,Yao; Shi,Guo‑Ming; Fan,Jia; Zhou,Jian; Huang,Xiao‑Wu

doi:10.3892/ol.2014.1809

2014-March Volume 7 Issue 3

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2014-March Volume 7 Issue 3

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Article

Prognostic significance of nuclear RNA export factor 3 in hepatocellular carcinoma

Authors:
- Jia‑Hao Jiang
- Qiang Gao
- Ai‑Wu Ke
- Yao Yu
- Guo‑Ming Shi
- Jia Fan
- Jian Zhou
- Xiao‑Wu Huang
View Affiliations / Copyright

Affiliations: Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai 200032, P.R. China
Pages: 641-646
|
Published online on: January 16, 2014

https://doi.org/10.3892/ol.2014.1809
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Abstract

Studies have highlighted important features of the nucleocytoplasmic transport of mRNAs and proteins. Nuclear RNA export factor 3 (NXF3) is a member of the nuclear RNA export factor family that plays a role in mediating the export of cellular mRNA from the nucleus to the cytoplasm for translation. However, little is known about the clinical significance of NXF3 in human tumors. To evaluate the prognostic significance of NXF3 in hepatocellular carcinoma (HCC), the expression levels of NXF3 in a cohort of 112 patients with primary HCC who had undergone hepatectomy for histologically confirmed HCC were assessed by immunohistochemistry. It was identified that the expression levels of NXF3 were higher in the primary HCC tissues compared with those in paired peritumoral liver tissues. The overexpression of NXF3 in the HCC tissues was correlated with decreased survival time [hazard ratio (HR) = 1.954, 95% confidence interval (CI) = 1.034‑3.695, P=0.039] and earlier tumor recurrence (HR = 2.101, 95% CI = 1.186‑3.722, P=0.011) in postoperative patients with HCC. Notably, overexpression of NXF3 was correlated with a poor survival time and increased recurrence following HCC resection in male patients (P=0.020 and P=0.007, respectively) but not in female patients (P=0.916 and P=0.821, respectively). In conclusion, the findings provide evidence that implicates NXF3 as a prospective predictor of HCC prognosis as well as a potential therapeutic target for cancer treatment.

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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
2	Maluccio M and Covey A: Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 62:394–399. 2012. View Article : Google Scholar
3	Grünwald D, Singer RH and Rout M: Nuclear export dynamics of RNA-protein complexes. Nature. 475:333–341. 2011.PubMed/NCBI
4	Siddiqui N and Borden KL: mRNA export and cancer. Wiley Interdiscip Rev RNA. 3:13–25. 2012. View Article : Google Scholar
5	Chow KH, Factor RE and Ullman KS: The nuclear envelope environment and its cancer connections. Nat Rev Cancer. 12:196–209. 2012.PubMed/NCBI
6	Yang J, Bogerd HP, Wang PJ, Page DC and Cullen BR: Two closely related human nuclear export factors utilize entirely distinct export pathways. Mol Cell. 8:397–406. 2001. View Article : Google Scholar
7	van der Watt PJ and Leaner VD: The nuclear exporter, Crm1, is regulated by NFY and Sp1 in cancer cells and repressed by p53 in response to DNA damage. Biochim Biophys Acta. 1809:316–326. 2011.PubMed/NCBI
8	Yin Y, Wang G, Liang N, et al: Nuclear export factor 3 is involved in regulating the expression of TGF-beta3 in an mRNA export activity-independent manner in mouse Sertoli cells. Biochem J. 452:67–78. 2013.PubMed/NCBI
9	Petrella BL, Armstrong DA and Vincenti MP: Interleukin-1 beta and transforming growth factor-beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 lung adenocarcinoma cells. Cancer Lett. 325:220–226. 2012. View Article : Google Scholar
10	Edge SB and Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
11	Edmondson HA and Steiner PE: Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 7:462–503. 1954. View Article : Google Scholar : PubMed/NCBI
12	Ke AW, Shi GM, Zhou J, et al: Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma. Hepatology. 49:491–503. 2009. View Article : Google Scholar
13	Cullen BR: Nuclear mRNA export: insights from virology. Trends Biochem Sci. 28:419–24. 2003. View Article : Google Scholar : PubMed/NCBI
14	Shen A, Wang Y, Zhao Y, Zou L, Sun L and Cheng C: Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery. 65:153–160. 2009. View Article : Google Scholar : PubMed/NCBI
15	van der Watt PJ, Maske CP, Hendricks DT, et al: The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 124:1829–1840. 2009.
16	Inoue H, Kauffman M, Shacham S, et al: CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth. J Urol. 189:2317–2326. 2013. View Article : Google Scholar : PubMed/NCBI
17	Lyon MF: Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 190:372–373. 1961. View Article : Google Scholar : PubMed/NCBI
18	Lyon MF: Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet. 14:135–148. 1962.PubMed/NCBI
19	Spatz A, Borg C and Feunteun J: X-chromosome genetics and human cancer. Nat Rev Cancer. 4:617–629. 2004. View Article : Google Scholar : PubMed/NCBI
20	Chen JG and Zhang SW: Liver cancer epidemic in China: past, present and future. Semin Cancer Biol. 21:59–69. 2011. View Article : Google Scholar : PubMed/NCBI
21	El-Serag HB and Rudolph KL: Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI
22	Wang N, Zheng Y, Yu X, Lin W, Chen Y and Jiang Q: Sex-modified effect of hepatitis B virus infection on mortality from primary liver cancer. Am J Epidemiol. 169:990–995. 2009. View Article : Google Scholar : PubMed/NCBI
23	Kau TR, Way JC and Silver PA: Nuclear transport and cancer: from mechanism to intervention. Nat Rev Cancer. 4:106–117. 2004. View Article : Google Scholar : PubMed/NCBI
24	van der Horst A and Burgering BM: Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 8:440–450. 2007.PubMed/NCBI
25	Kau TR, Schroeder F, Ramaswamy S, et al: A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells. Cancer Cell. 4:463–476. 2003. View Article : Google Scholar
26	Sakakibara K, Saito N, Sato T, et al: CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity. Blood. 118:3922–3931. 2011. View Article : Google Scholar : PubMed/NCBI
27	Mao L and Yang Y: Targeting the nuclear transport machinery by rational drug design. Curr Pharm Des. 19:2318–2325. 2013. View Article : Google Scholar : PubMed/NCBI