Upstream transcription factor 1 prompts malignancies of cervical cancer primarily by transcriptionally activating p65 expression Retraction in /10.3892/etm.2024.12631

Wang,Wen; Yao,Shujuan; Jiang,Hongjing; Dong,Jing; Cui,Xiujuan; Tian,Xiangyu; Guo,Yanyan; Zhang,Shiqian

doi:10.3892/etm.2018.6758

Upstream transcription factor 1 prompts malignancies of cervical cancer primarily by transcriptionally activating p65 expression

Retraction in: /10.3892/etm.2024.12631

Authors:
- Wen Wang
- Shujuan Yao
- Hongjing Jiang
- Jing Dong
- Xiujuan Cui
- Xiangyu Tian
- Yanyan Guo
- Shiqian Zhang
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Affiliations: Department of Obstetrics and Gynecology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Medical Imaging, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Department of Obstetrics and Gynecology, Shandong Police Hospital, Jinan, Shandong 250001, P.R. China, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: September 18, 2018 https://doi.org/10.3892/etm.2018.6758
Pages: 4415-4422
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cervical cancer is the third‑most common cause of female cancer‑related mortality worldwide. In cervical cancer, aberrant activation of nuclear factor (NF)‑κB signaling is widely reported. However, the transcriptional regulation of NF‑κB signaling remains unclear. The present study aimed to explore the underlying mechanism in which NF‑κB signaling was activated in cervical cancer cells. Initially, the expression of p65 was demonstrated to be markedly enhanced in grade II, III or IV cervical cancer tissues compared with that of normal cervical tissues, indicating that p65 expression was correlated with tumor grade. In HeLa and CaSki cells, overexpression of p65 markedly enhanced cervical cancer cell invasion and migration. Further experiments demonstrated that p65 overexpression significantly increased the phosphorylation levels of protein kinase B (AKT) and p38. Dual luciferase reporter and chromatin immunoprecipitation assays demonstrated that USF1 was able to bind the promoter region of p65, thereby enhancing the transcriptional activation of p65. Notably, when p65 was silenced, the phosphorylation levels of AKT and p38 were suppressed even in cells transfected with adenovirus vectors expressing upstream transcription factor 1 (USF1). These data indicated that USF1 prompted cervical cancer progression primarily by transcriptionally activating p65. In conclusion, the present study demonstrated that USF1 was able to activate the transcription of p65, thereby enhancing the malignancy of cervical cancer cells.

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1	Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ and Naghavi M: Breast and cervical cancer in 187 countries between 1980 and 2010: A systematic analysis. Lancet. 378:1461–1484. 2011. View Article : Google Scholar : PubMed/NCBI
2	Bian ML, Cheng JY, Ma L, Cong X, Liu J, Chen Y and Chen X: Evaluation of the detection of 14 high-risk human papillomaviruses with HPV 16 and HPV 18 genotyping for cervical cancer screening. Exp Ther Med. 6:1332–1336. 2013. View Article : Google Scholar : PubMed/NCBI
3	Chao A, Lin CT and Lai CH: Updates in systemic treatment for metastatic cervical cancer. Curr Treat Options Oncol. 15:1–13. 2014. View Article : Google Scholar : PubMed/NCBI
4	Lu X, Wu L, Liu Z, Xie L and Wang S: Peripheral blood mononuclear cells inhibit proliferation and promote apoptosis of HeLa cells following stimulation with Bacillus Calmette-Guerin. Exp Ther Med. 5:561–566. 2013. View Article : Google Scholar : PubMed/NCBI
5	Nartthanarung A, Thanapprapasr K, Udomsubpayakul U and Thanapprapasr D: Age and survival of cervical cancer patients with bone metastasis. Asian Pac J Cancer Prev. 15:8401–8404. 2014. View Article : Google Scholar : PubMed/NCBI
6	Thanapprapasr D, Nartthanarung A, Likittanasombut P, Ayudhya Na NI, Charakorn C, Udomsubpayakul U, Subhadarbandhu T and Wilailak S: Bone metastasis in cervical cancer patients over a 10-year period. Int J Gynecol Cancer. 20:373–378. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hyldahl RD, Schwartz LM and Clarkson PM: NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation. Muscle Nerve. 47:522–531. 2013. View Article : Google Scholar : PubMed/NCBI
8	Limpert AS, Bai S, Narayan M, Wu J, Yoon SO, Carter BD and Lu QR: NF-kB forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation. J Neurosci. 33:2388–2397. 2013. View Article : Google Scholar : PubMed/NCBI
9	Zhou R, Hu G, Gong AY and Chen XM: Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res. 38:3222–3232. 2010. View Article : Google Scholar : PubMed/NCBI
10	Pfeffer LM: The role of nuclear factor kappaB in the interferon response. J Interferon Cytokine Res. 31:553–559. 2011. View Article : Google Scholar : PubMed/NCBI
11	Karin M, Cao Y, Greten FR and Li ZW: NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI
12	Wang CY, Cusack JC Jr, Liu R and Baldwin AS Jr: Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med. 5:412–417. 1999. View Article : Google Scholar : PubMed/NCBI
13	He A, Ji R, Shao J, He C, Jin M and Xu Y: TLR4-MyD88-TRAF6-TAK1 Complex-Mediated NF-kB Activation Contribute to the Anti-inflammatory effect of V8 in LPS-induced human cervical cancer SiHa cells. Inflammation. 39:172–181. 2016. View Article : Google Scholar : PubMed/NCBI
14	Ma XF, Zhang J, Shuai HL, Guan BZ, Luo X and Yan RL: IKKβ/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells. Arch Biochem Biophys. 573:52–58. 2015. View Article : Google Scholar : PubMed/NCBI
15	Pajukanta P, Lilja HE, Sinsheimer JS, Cantor RM, Lusis AJ, Gentile M, Duan XJ, Soro-Paavonen A, Naukkarinen J, Saarela J, et al: Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nat Genet. 36:371–376. 2004. View Article : Google Scholar : PubMed/NCBI
16	Plaisier CL, Horvath S, Huertas-Vazquez A, Cruz-Bautista I, Herrera MF, Tusie-Luna T, Aguilar-Salinas C and Pajukanta P: A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia. PLoS Genet. 5:e10006422009. View Article : Google Scholar : PubMed/NCBI
17	Meex SJ, van Vliet-Ostaptchouk JV, van der Kallen CJ, van Greevenbroek MM, Schalkwijk CG, Feskens EJ, Blaak EE, Wijmenga C, Hofker MH, Stehouwer CD and de Bruin TW: Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: Association study in 2000 Dutch caucasians. Mol Genet Metab. 94:352–355. 2008. View Article : Google Scholar : PubMed/NCBI
18	Benedet JL, Bender H, Jones H III, Ngan HY and Pecorelli S: FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 70:209–262. 2000. View Article : Google Scholar : PubMed/NCBI
19	Coulson JM, Edgson JL, Marshall-Jones ZV, Mulgrew R, Quinn JP and Woll PJ: Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box. Biochem J. 369:549–561. 2003. View Article : Google Scholar : PubMed/NCBI
20	Chen B, Hsu R, Li Z, Kogut PC, Du Q, Rouser K, Camoretti-Mercado B and Solway J: Upstream stimulatory factor 1 activates GATA5 expression through an E-box motif. Biochem J. 446:89–98. 2012. View Article : Google Scholar : PubMed/NCBI
21	Pahne-Zeppenfeld J, Schroer N, Walch-Ruckheim B, Oldak M, Gorter A, Hegde S and Smola S: Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells. Int J Cancer. 134:2061–2073. 2014. View Article : Google Scholar : PubMed/NCBI
22	Sun S, Tang L, Zhang J, Lv F, Wang Z, Wang L, Zhang Q, Zheng C, Qiu L, Jia Z, et al: Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer. Int J Nanomedicine. 9:1443–1452. 2014.PubMed/NCBI
23	Xu L, Liu JH, Zhang J and Wang ZH: Blockade of autophagy aggravates endoplasmic reticulum stress and improves Paclitaxel cytotoxicity in human cervical cancer cells. Cancer Res Treat. 47:313–321. 2015. View Article : Google Scholar : PubMed/NCBI
24	Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest. 107:241–246. 2001. View Article : Google Scholar : PubMed/NCBI
25	Li J, Jia H, Xie L, Wang X, Wang X, He H, Lin Y and Hu L: Association of constitutive nuclear factor-kappaB activation with aggressive aspects and poor prognosis in cervical cancer. Int J Gynecol Cancer. 19:1421–1426. 2009. View Article : Google Scholar : PubMed/NCBI
26	Chou RH, Hsieh SC, Yu YL, Huang MH, Huang YC and Hsieh YH: Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway. PLoS One. 8:e719832013. View Article : Google Scholar : PubMed/NCBI
27	Park BK, Zhang H, Zeng Q, Dai J, Keller ET, Giordano T, Gu K, Shah V, Pei L, Zarbo RJ, et al: NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med. 13:62–69. 2007. View Article : Google Scholar : PubMed/NCBI
28	Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J and Liu JR: Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complement Altern Med. 7:442007. View Article : Google Scholar : PubMed/NCBI
29	Zong H, Wang F, Fan QX and Wang LX: Curcumin inhibits metastatic progression of breast cancer cell through suppression of urokinase-type plasminogen activator by NF-kappa B signaling pathways. Mol Biol Rep. 39:4803–4808. 2012. View Article : Google Scholar : PubMed/NCBI
30	Sahu BD, Kumar JM and Sistla R: Fisetin, a dietary flavonoid, ameliorates experimental colitis in mice: Relevance of NF-κB signaling. J Nutr Biochem. 28:171–182. 2016. View Article : Google Scholar : PubMed/NCBI
31	Yuan Q, Bu Q, Li G, Zhang J, Cui T, Zhu R and Mu D: Association between single nucleotide polymorphisms of upstream transcription factor 1 (USF1) and susceptibility to papillary thyroid cancer. Clin Endocrinol (Oxf). 84:564–570. 2016. View Article : Google Scholar : PubMed/NCBI
32	Landa I, Ruiz-Llorente S, Montero-Conde C, Inglada-Pérez L, Schiavi F, Leskelä S, Pita G, Milne R, Maravall J, Ramos I, et al: The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS Genet. 5:e10006372009. View Article : Google Scholar : PubMed/NCBI