LncRNA HOXD-AS1 Is Upregulated in Ovarian Cancer

Document Type : Research Articles

Authors

• Seyedeh Nahid Fotuhi ¹
• Mohammad Khalaj-Kondori ¹
• Hadis Karimi ²

¹ Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran

² Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

https://doi.org/10.22067/jcmr.2021.67052.0

Abstract

     Patients with ovarian cancer are mostly diagnosed at advanced stages which leads to poor prognosis and high mortality rate. Deregulation of lncRNA HOXD-AS1 expression associates with cancer development and metastasis. However, the expression level of this lncRNA in ovarian cancer is not determined.50paired ovarian tumors and their adjusted normal tissues were included in the study. Total RNA was extracted by TRIzol^® Reagent and reverse-transcribed to cDNA using PrimeScript II cDNA synthesis kit. The expression levels of HOXD-AS1 were quantified by qRT-PCR and compared. The Roc curve analysis was used to evaluate the capacity of HOXD-AS1 as a biomarker for ovarian cancer. We observed that lncRNA HOXD-AS1 was significantly upregulated in ovarian tumors compared to their adjusted normal tissues (p <0.003). Moreover, the ROC curve analysis revealed that the lncRNA HOXD-AS1 expression level could discriminate tumoral and non-tumoral tissues with 85% sensitivity and 88% specificity. The lncRNA HOXD-AS1 expression level might be considered as a potential biomarker for ovarian cancer development.  

Keywords

• Ovarian cancer
• Biomarker
• lncRNA
• HOXD-AS1
• Gene expression

20.1001.1.20089147.2021.12.2.1.3

References

Bignotti E., Tassi R. A., Calza S., Ravaggi A., Romani C., Rossi E., et al. (2006) Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: identification of novel molecular biomarkers for early diagnosis and therapy. Gynecologic oncology 103:405-416.

Chi J.-s., Li J.-z., Jia J.-j., Zhang T., Liu X.-m., and Yi, L. (2017). Long non-coding RNA ANRIL in gene regulation and its duality in atherosclerosis. Current Medical Science 37: 816-822.

Ditto A., Leone Roberti Maggiore U., Bogani G., Martinelli F., Chiappa V., Evangelista M. T., et al. (2019). Predictive factors of recurrence in patients with early‐stage epithelial ovarian cancer. International Journal of Gynecology & Obstetrics 145:28-33.

Dochez V., Caillon H., Vaucel E., Dimet J., Winer N., and Ducarme G. (2019). Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. Journal of ovarian research 12:28.

Dong S., Wang R., Wang H., Ding Q., Zhou X., Wang J.,et al. (2019). HOXD-AS1 promotes the epithelial to mesenchymal transition of ovarian cancer cells by regulating miR-186-5p and PIK3R3. Journal of Experimental & Clinical Cancer Research 38:110.

Fang Y., and Fullwood M. J. (2016). Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genomics, proteomics & bioinformatics 14: 42-54.

Fiegl H., Windbichler G., Mueller‐Holzner E., Goebel G., Lechner M., Jacobs I. J., and Widschwendter M. (2008). HOXA11 DNA methylation—a novel prognostic biomarker in ovarian cancer. International journal of cancer 123: 725-729.

Goode E. L., Chenevix-Trench G., Song H., Ramus S. J., Notaridou M., Lawrenson K., et al. (2010). A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nature genetics 42: 874-879.

Jacobs I., and Bast Jr R. C. (1989). The CA 125 tumour-associated antigen: a review of the literature. Human reproduction 4: 1-12.

Knutson K. L., Karyampudi L., Lamichhane P., and Preston C. (2015). RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer. Cancer and Metastasis Reviews 34: 53-74.

La Vecchia C. (2001). Epidemiology of ovarian cancer: a summary review. European Journal of Cancer Prevention 10: 125-129.

LaDuca H., Polley E. C., Yussuf A., Hoang L., Gutierrez S., Hart S. N.,et al. (2019). A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients. Genetics in Medicine, 1-9.

Larman H. B., Zhao Z., Laserson U., Li M. Z., Ciccia A., Gakidis M. A. M., et al. (2011). Autoantigen discovery with a synthetic human peptidome. Nature biotechnology 29: 535-541.

Li L., Wang Y., Song, G., Zhang X., Gao S., and Liu H. (2019). HOX cluster-embedded antisense long non-coding RNAs in lung cancer. Cancer letters 450:14-21.

Liu R., Wang X., Aihara K., & Chen L. (2014). Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers. Medicinal research reviews 34, 455-478.

Livak K. J., and Schmittgen T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods 25:402-408.

Momenimovahed Z., Tiznobaik A., Taheri S., and Salehiniya H. (2019). Ovarian cancer in the world: epidemiology and risk factors. International journal of women's health 11:287.

Prensner J. R., Iyer M. K., Sahu A., Asangani I. A., Cao Q., Patel L., et al. (2013). The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nature genetics 45:1392.

Qu C., Dai C., Guo Y., Qin R., and Liu J. (2019). Long noncoding RNA SNHG15 serves as an oncogene and predicts poor prognosis in epithelial ovarian cancer. OncoTargets and therapy 12, 101.

Razi S., Ghoncheh M., Mohammadian-Hafshejani A., Aziznejhad H., Mohammadian M., and Salehiniya H. (2016). The incidence and mortality of ovarian cancer and their relationship with the Human Development Index in Asia. ecancermedicalscience 10.

Russell M. R., Graham C., D’Amato A., Gentry-Maharaj A., Ryan A., Kalsi J. K.,et al. (2019). Diagnosis of epithelial ovarian cancer using a combined protein biomarker panel. British journal of cancer 121: 483.

Sheng R., Li X., Wang Z., and Wang X. (2020). Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer. Cancer Letters 473:139-147.

Soshnikova N., and Duboule D. (2009). Epigenetic temporal control of mouse Hox genes in vivo. Science 324: 1320-1323.

Taylor D. D., and Gercel-Taylor C. (2008). MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecologic oncology 110:13-21.

Vosseler S., Lederle W., Airola K., Obermueller E., Fusenig, N. E., and Mueller M. M. (2009). Distinct progression‐associated expression of tumor and stromal MMPs in HaCaT skin SCCs correlates with onset of invasion. International journal of cancer 125: 2296-2306.

Wang H., Huo X., Yang X.-R., He,J., Cheng,L., Wang N.,et al. (2017). STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Molecular cancer 16: 136.

Wang Y., Zhang W., Wang Y., and Wang S. (2018). HOXD-AS1 promotes cell proliferation, migration and invasion through miR-608/FZD4 axis in ovarian cancer. American journal of cancer research 8: 170.

Xie S., Yang Y., Zhang J., Zhou S., Xie S., and Hua Y. (2019). HOXD-AS1: a novel oncogenic long intergenic non-coding RNA in humans. European review for medical and pharmacological sciences 23: 2898-2907.

Yaginuma Y., Yamashita K., Kuzumaki N., Fujita M., and Shimizu T. (1992). ras oncogene product p21 expression and prognosis of human ovarian tumors. Gynecologic oncology 46: 45-50.

Yang L., Lin C., Jin C., Yang J. C., Tanasa B., Li W., et al. (2013). lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature 500: 598-602.

Yarmishyn A. A., Batagov A. O., Tan J. Z., Sundaram G. M., Sampath P., Kuznetsov V. A., and Kurochkin I. V. (2014). HOXD-AS1 is a novel lncRNA encoded in HOXD cluster and a marker of neuroblastoma progression revealed via integrative analysis of noncoding transcriptome. BMC genomics 15: S7.

Yuan D., Zhang X., Zhao Y., Qian H., Wang H., He C., et al. (2020). Role of lncRNA‑ATB in ovarian cancer and its mechanisms of action. Experimental and Therapeutic Medicine 19: 965-971.

Yuan J.-h., Yang F., Wang F., Ma J.-z., Guo Y.-j., Tao Q.-f., et al. (2014). A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer cell 25: 666-681.

Zhang B., Cai F. F., and Zhong X. Y. (2011). An overview of biomarkers for the ovarian cancer diagnosis. European Journal of Obstetrics & Gynecology and Reproductive Biology 158: 119-123.

Zhang Y., Dun Y., Zhou S., and Huang X.-H. (2017). LncRNA HOXD-AS1 promotes epithelial ovarian cancer cells proliferation and invasion by targeting miR-133a-3p and activating Wnt/β-catenin signaling pathway. Biomedicine & Pharmacotherapy 96: 1216-1221.

Zhang Y., Luo G., Li M., Guo P., Xiao Y., Ji H., and Hao Y. (2019). Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis. BMC cancer 19: 984.

Zou A., Liu R., and Wu X. (2016). Long non-coding RNA MALAT1 is up-regulated in ovarian cancer tissue and promotes SK-OV-3 cell proliferation and invasion. Neoplasma 63, 865.