Survival‑related DLEU1 is associated with HPV infection status and serves as a biomarker in HPV‑infected cervical cancer

Dong,Aiping; Xu,Bin; Wang,Zhanzhao; Miao,Xia

doi:10.3892/mmr.2022.12593

Survival‑related DLEU1 is associated with HPV infection status and serves as a biomarker in HPV‑infected cervical cancer

Authors:
- Aiping Dong
- Bin Xu
- Zhanzhao Wang
- Xia Miao
View Affiliations

Affiliations: Department of Clinical Laboratory, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Clinical Laboratory, Weifang Center for Disease Control and Prevention, Weifang, Shandong 261061, P.R. China
Published online on: January 10, 2022 https://doi.org/10.3892/mmr.2022.12593
Article Number: 77
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Human papillomavirus (HPV) is the most common risk factor for the occurrence of cervical cancer (CC). In recent years, the important roles of long non‑coding RNAs (lncRNAs) in CC have emerged, but studies on the relationship between lncRNAs and HPV‑positive (HPV+) CC remain scarce. The present study aimed to investigate whether lncRNA deleted in lymphocytic leukemia 1 (DLEU1) is associated with HPV infection and explore the clinical significance of DLEU1 in HPV+ patients with CC. DLEU1 expression was detected by reverse transcription‑quantitative PCR. The ability of DLEU1 to screen patients with CC from controls and differentiate individuals with different HPV infection status was evaluated by receiver operating characteristic analysis. The association of DLEU1 with the survival prognosis of patients with CC was assessed by Kaplan‑Meier survival analysis and Cox regression analysis. The RNA Interactome Database was used to predict molecules interacting with DLEU1. The results indicated that DLEU1 expression was significantly upregulated in CC tissues and cell lines, particularly in those that were HPV+. In addition, DLEU1 had a high diagnostic value in discriminating patients with CC and differentiating between HPV+ and HPV‑ patients with CC, and had a certain ability to screen HPV+ controls. DLEU1 was correlated with HPV infection in CC patients. Furthermore, DLEU1 was indicated to be associated with survival prognosis in both total patients with CC and HPV+ patients with CC, and independently predict the prognosis of patients with CC. Most of the molecules interacting with DLEU1 were microRNAs. In conclusion, abnormal DLEU1 expression is associated with HPV infection and may serve as a diagnostic and prognostic biomarker for HPV+ patients with CC.

View Figures

View References

1	Pourhanifeh MH, Darvish M, Tabatabaeian J, Fard MR, Mottaghi R, Azadchehr MJ, Jahanshahi M, Sahebkar A and Mirzaei H: Therapeutic role of curcumin and its novel formulations in gynecological cancers. J Ovarian Res. 13:1302020. View Article : Google Scholar : PubMed/NCBI
2	Nahand JS, Vandchali NR, Darabi H, Doroudian M, Banafshe HR, Moghoofei M, Babaei F, Salmaninejad A and Mirzaei H: Exosomal microRNAs: Novel players in cervical cancer. Epigenomics. 12:1651–1660. 2020. View Article : Google Scholar : PubMed/NCBI
3	Sadri Nahand J, Moghoofei M, Salmaninejad A, Bahmanpour Z, Karimzadeh M, Nasiri M, Mirzaei HR, Pourhanifeh MH, Bokharaei-Salim F, Mirzaei H, et al: Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review. Int J Cancer. 146:305–320. 2020. View Article : Google Scholar : PubMed/NCBI
4	Yu F, Liu J, Dong W, Xie J and Zhao X: The diagnostic value of miR-145 and miR-205 in patients with cervical cancer. Am J Transl Res. 13:1825–1832. 2021.PubMed/NCBI
5	Yang PM, Chou CJ, Tseng SH and Hung CF: Bioinformatics and in vitro experimental analyses identify the selective therapeutic potential of interferon gamma and apigenin against cervical squamous cell carcinoma and adenocarcinoma. Oncotarget. 8:46145–46162. 2017. View Article : Google Scholar : PubMed/NCBI
6	Park S, Eom K, Kim J, Bang H, Wang HY, Ahn S, Kim G, Jang H, Kim S, Lee D, et al: MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer. BMC Cancer. 17:6582017. View Article : Google Scholar : PubMed/NCBI
7	Causin RL, da Silva LS, Evangelista AF, Leal LF, Souza KC, Pessôa-Pereira D, Matsushita GM, Reis RM, Fregnani JH and Marques MM: MicroRNA biomarkers of high-grade cervical intraepithelial neoplasia in liquid biopsy. BioMed Res Int. 2021:66509662021. View Article : Google Scholar : PubMed/NCBI
8	Boscolo-Rizzo P, Furlan C, Lupato V, Polesel J and Fratta E: Novel insights into epigenetic drivers of oropharyngeal squamous cell carcinoma: Role of HPV and lifestyle factors. Clin Epigenetics. 9:1242017. View Article : Google Scholar : PubMed/NCBI
9	Zamani S, Sohrabi A, Hosseini SM, Rahnamaye-Farzami M and Akbari A: Deregulation of miR-21 and miR-29a in Cervical Cancer Related to HPV Infection. MicroRNA. 8:110–115. 2019. View Article : Google Scholar : PubMed/NCBI
10	Li J, Chu ZP, Han H, Zhang Y, Tian F, Zhang JQ and Huang XH: Suppression of miR-93-5p inhibits high-risk HPV-positive cervical cancer progression via targeting of BTG3. Hum Cell. 32:160–171. 2019. View Article : Google Scholar : PubMed/NCBI
11	Nohata N, Abba MC and Gutkind JS: Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection. Oral Oncol. 59:58–66. 2016. View Article : Google Scholar : PubMed/NCBI
12	Razavi ZS, Asgarpour K, Mahjoubin-Tehran M, Rasouli S, Khan H, Shahrzad MK, Hamblin MR and Mirzaei H: Angiogenesis-related non-coding RNAs and gastrointestinal cancer. Mol Ther Oncolytics. 21:220–241. 2021. View Article : Google Scholar : PubMed/NCBI
13	Mahjoubin-Tehran M, Rezaei S, Jesmani A, Birang N, Morshedi K, Khanbabaei H, Khan H, Piranviseh A, Nejati M, Aschner M, et al: New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs. Biomed Pharmacother. 140:1117532021. View Article : Google Scholar : PubMed/NCBI
14	Shafabakhsh R, Arianfar F, Vosough M, Mirzaei HR, Mahjoubin-Tehran M, Khanbabaei H, Kowsari H, Shojaie L, Azar ME, Hamblin MR, et al: Autophagy and gastrointestinal cancers: The behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance. Cancer Gene Ther. Jan 11–2021.(Epub ahead of print). doi: 10.1038/s41417-020-00272-7. View Article : Google Scholar : PubMed/NCBI
15	Mirzaei H and Hamblin MR: Regulation of glycolysis by non-coding RNAs in cancer: Switching on the Warburg effect. Mol Ther Oncolytics. 19:218–239. 2020. View Article : Google Scholar : PubMed/NCBI
16	Hashemian SM, Pourhanifeh MH, Fadaei S, Velayati AA, Mirzaei H and Hamblin MR: Non-coding RNAs and exosomes: their role in the pathogenesis of sepsis. Mol Ther Nucleic Acids. 21:51–74. 2020. View Article : Google Scholar : PubMed/NCBI
17	Hashemipour M, Boroumand H, Mollazadeh S, Tajiknia V, Nourollahzadeh Z, Rohani Borj M, Pourghadamyari H, Rahimian N, Hamblin MR and Mirzaei H: Exosomal microRNAs and exosomal long non-coding RNAs in gynecologic cancers. Gynecol Oncol. 161:314–327. 2021. View Article : Google Scholar : PubMed/NCBI
18	Rahimian N, Razavi ZS, Aslanbeigi F, Mirkhabbaz AM, Piroozmand H, Shahrzad MK, Hamblin MR and Mirzaei H: Non-coding RNAs related to angiogenesis in gynecological cancer. Gynecol Oncol. 161:896–912. 2021. View Article : Google Scholar : PubMed/NCBI
19	Razavi ZS, Tajiknia V, Majidi S, Ghandali M, Mirzaei HR, Rahimian N, Hamblin MR and Mirzaei H: Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles. Crit Rev Oncol Hematol. 157:1031922021. View Article : Google Scholar : PubMed/NCBI
20	Liu C, Tian X, Zhang J and Jiang L: Long Non-coding RNA DLEU1 promotes proliferation and invasion by interacting with miR-381 and enhancing HOXA13 expression in cervical cancer. Front Genet. 9:6292018. 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	Lv QL, Wang LC, Li DC, Lin QX, Shen XL, Liu HY, Li M, Ji YL, Qin CZ and Chen SH: Knockdown lncRNA DLEU1 inhibits gliomas progression and promotes temozolomide chemosensitivity by regulating autophagy. Front Pharmacol. 11:5605432020. View Article : Google Scholar : PubMed/NCBI
23	Shan L, Zhao T and Wang Y: Upregulation of Serum lncRNA DLEU1 predicts progression of premalignant endometrial lesion and unfavorable clinical outcome of endometrial cancer. Technol Cancer Res Treat. Dec 17–2020.(Epub ahead of print). doi: 10.1177/1533033820965589. View Article : Google Scholar
24	Lv T, Liu H, Wu Y and Huang W: Knockdown of lncRNA DLEU1 inhibits the tumorigenesis of oral squamous cell carcinoma via regulation of miR-149 5p/CDK6 axis. Mol Med Rep. 23:4472021. View Article : Google Scholar : PubMed/NCBI
25	Kopczyńska M, Kolenda T, Guglas K, Sobocińska J, Teresiak A, Bliźniak R, Mackiewicz A, Mackiewicz J and Lamperska K: PRINS lncRNA is a new biomarker candidate for HPV infection and prognosis of head and neck squamous cell carcinomas. Diagnostics (Basel). 10:E7622020. View Article : Google Scholar
26	Zhou D, Wu F, Cui Y, Wei F, Meng Q and Lv Q: Long non-coding RNA-OIS1 inhibits HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1. Oncol Lett. 17:2923–2930. 2019.PubMed/NCBI
27	Zhang Y, Jia LG, Wang P, Li J, Tian F, Chu ZP and Kang S: The expression and significance of lncRNA HOST2 and microRNA let-7b in HPV-positive cervical cancer tissues and cell lines. Eur Rev Med Pharmacol Sci. 23:2380–2390. 2019.PubMed/NCBI
28	Iancu IV, Anton G, Botezatu A, Huica I, Nastase A, Socolov DG, Stanescu AD, Dima SO, Bacalbasa N and Plesa A: LINC01101 and LINC00277 expression levels as novel factors in HPV-induced cervical neoplasia. J Cell Mol Med. 21:3787–3794. 2017. View Article : Google Scholar : PubMed/NCBI
29	Fattahi S, Nikbakhsh N, Taheri H, Ghadami E, Ranaee M and Akhavan-Niaki H: LINC02688 and PP7080 as novel biomarkers in early diagnosis of gastric cancer. Noncoding RNA Res. 6:86–91. 2021. View Article : Google Scholar : PubMed/NCBI
30	Zhang Y, Sun Y, Ding L, Shi W, Ding K and Zhu Y: Long non-coding RNA LINC00467 correlates to poor prognosis and aggressiveness of breast cancer. Front Oncol. 11:6433942021. View Article : Google Scholar : PubMed/NCBI
31	Chao Y and Zhou D: lncRNA-D16366 is a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma. Med Sci Monit. 25:6581–6586. 2019. View Article : Google Scholar : PubMed/NCBI
32	Du P, Zhi Y, Wang R, Li Y, Li H, Zhang X, Cheng G and Li X: Aberrant methylation of the SOX21-AS1 promoter region promotes gene expression and its clinical value in cervical cancer. Reprod Sci. 28:532–540. 2021. View Article : Google Scholar : PubMed/NCBI
33	Zhang J, Jiang P, Wang S, Cheng W and Fu S: LncRNA LIPE-AS1 predicts poor survival of cervical cancer and promotes its proliferation and migration via modulating miR-195-5p/MAPK pathway. Front Oncol. 11:6399802021. View Article : Google Scholar : PubMed/NCBI
34	Wang J, Zhang Y, Lin R, Mao B, Wang W, Bai Y, He W and Liu Q: Long noncoding RNA loc285194 expression in human papillomavirus-positive and -negative cervical squamous cell carcinoma, C33A, and SiHa cells and transforming growth factor-β1. Med Sci Monit. 25:9012–9018. 2019. View Article : Google Scholar : PubMed/NCBI
35	Jin L, Ji J, Shi L, Jin S and Pei L: lncRNA HAND2-AS1 inhibits cancer cell proliferation, migration and invasion by downregulating ROCK1 in HPV-positive and negative cervical squamous cell carcinoma. Exp Ther Med. 18:2512–2518. 2019.PubMed/NCBI
36	Liu Y, Li M, Yu H and Piao H: LncRNA SRA1 is down-regulated in HPV-negative cervical squamous cell carcinoma and regulates cancer cell behaviors. Biosci Rep. Aug 15–2019.(Epub ahead of print). doi: 10.1042/BSR20191226.
37	Cao Y, Yang R, Lee I, Zhang W, Sun J, Meng X and Wang W: Prediction of LncRNA-encoded small peptides in glioma and oligomer channel functional analysis using in silico approaches. PLoS One. 16:e02486342021. View Article : Google Scholar : PubMed/NCBI
38	Wang C, Xie XX, Li WJ and Jiang DQ: LncRNA DLEU1/microRNA-300/RAB22A axis regulates migration and invasion of breast cancer cells. Eur Rev Med Pharmacol Sci. 23:10410–10421. 2019.PubMed/NCBI
39	Zhang X, Wang Y, Zhao A, Kong F, Jiang L and Wang J: Long Non-coding RNA LINC00511 accelerates proliferation and invasion in cervical cancer through targeting miR-324-5p/DRAM1 axis. OncoTargets Ther. 13:10245–10256. 2020. View Article : Google Scholar : PubMed/NCBI
40	Liu S, Song L, Zeng S and Zhang L: MALAT1-miR-124-RBG2 axis is involved in growth and invasion of HR-HPV-positive cervical cancer cells. Tumour Biol. 37:633–640. 2016. View Article : Google Scholar : PubMed/NCBI
41	Jiang S, Qi Y, He R, Huang Y, Liu Z, Ma Y, Guo X, Shao Y, Sun Z and Ruan Q: Human cytomegalovirus microRNA miR-US25-1-5p inhibits viral replication by targeting multiple cellular genes during infection. Gene. 570:108–114. 2015. View Article : Google Scholar : PubMed/NCBI
42	Broccolo F, Cassina G, Chiari S, Garcia-Parra R, Villa A, Leone BE, Brenna A, Locatelli G, Mangioni C and Cocuzza CE: Frequency and clinical significance of human beta-herpesviruses in cervical samples from Italian women. J Med Virol. 80:147–153. 2008. View Article : Google Scholar : PubMed/NCBI