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Erschienen in: Journal of Gastrointestinal Cancer 1/2022

10.11.2020 | Original Research

Overexpression of HOXA-AS2 LncRNA in Patients with Gastric Cancer and Its Association with Helicobacter pylori Infection

verfasst von: Ali Rajabi, Atousa Riahi, Hanie Shirabadi-Arani, Yaghoub Moaddab, Mehdi Haghi, Reza Safaralizadeh

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1/2022

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Abstract

Purpose

LncRNAs are regulatory factors that play a prominent role in the carcinogenesis processes and cancer cell ability to invade and metastasize. Hence, lncRNAs are considered as the potential diagnostic and therapeutic biomarkers in diverse malignancies. The present study was designed to assess the difference of HOXA-AS2 gene expression levels in cancerous tissues as compared to marginal noncancerous tissues of gastric cancer patients.

Methods

Fifty pairs of cancerous and marginal noncancerous tissue of gastric cancer patients were collected in the present study. Then, RNA extraction and cDNA synthesis were performed for all specimens. The qRT-PCR was carried out to examine the difference of HOXA-AS2 gene expression. Furthermore, the association between HOXA-AS2 expression and the clinicopathological features as well as the function of HOXA-AS2 biomarkers was evaluated.

Results

The HOXA-AS2 expression was significantly elevated in cancerous tissues as compared to marginal noncancerous tissues in gastric cancer patients (p < 0.0001). Analysis of gene expression data revealed that there was a significant association between an increased HOXA-AS2 gene expression and clinicopathological features such as tumor size ˃ 5 cm (p = 0.009), lymph node metastasis (p = 0.028), and H. pylori infection (p = 0.011). The results of ROC analysis indicated that HOXA-AS2 with AUC, sensitivity, and specificity of 0.816, 92%, and 70%, respectively, can act as a potential biomarker (CI 95% = 0.7297–0.9023).

Conclusion

With regard to the overexpression of HOXA-AS2 in gastric cancer tissues, the mentioned gene may serve as an oncogenic lncRNA in gastric cancer patients. Moreover, HOXA-AS2 can act as a potential biomarker in molecular targeted therapies to recognize and treat gastric cancer patients.
Literatur
2.
Zurück zum Zitat Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics, and treatment strategies. Int J Mol Sci. 2020;21(11):4012.CrossRef Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics, and treatment strategies. Int J Mol Sci. 2020;21(11):4012.CrossRef
3.
Zurück zum Zitat Teresa F, Serra N, Capra G, et al. Helicobacter pylori and Epstein-Barr virus infection in gastric diseases: correlation with IL-10 and IL1RN polymorphism. J Oncol. 2019;2019:1785132.CrossRef Teresa F, Serra N, Capra G, et al. Helicobacter pylori and Epstein-Barr virus infection in gastric diseases: correlation with IL-10 and IL1RN polymorphism. J Oncol. 2019;2019:1785132.CrossRef
4.
Zurück zum Zitat Zhong X, Yu X, Wen X, Chen L, Gu N. Activation of the LINC00242/miR-141/FOXC1 axis underpins the development of gastric cancer. Cancer Cell Int. 2020;20:272.CrossRef Zhong X, Yu X, Wen X, Chen L, Gu N. Activation of the LINC00242/miR-141/FOXC1 axis underpins the development of gastric cancer. Cancer Cell Int. 2020;20:272.CrossRef
5.
Zurück zum Zitat Lian Y, Yan C, Lian Y, Yang R, Chen Q, Ma D, et al. Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1. Cell Death Dis. 2020;11(7):522.CrossRef Lian Y, Yan C, Lian Y, Yang R, Chen Q, Ma D, et al. Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1. Cell Death Dis. 2020;11(7):522.CrossRef
6.
Zurück zum Zitat Mohammadzadeh A, Baradaran B, Dastmalchi N, Hashemzadeh S, Safaralizadeh R. The correlation between Helicobacter pylori infection and Lnc-OC1 expression in gastric cancer tissues in an Iranian population. J Gastrointest Cancer. 2020. https://doi.org/10.1007/s12029-020-00438-4. Mohammadzadeh A, Baradaran B, Dastmalchi N, Hashemzadeh S, Safaralizadeh R. The correlation between Helicobacter pylori infection and Lnc-OC1 expression in gastric cancer tissues in an Iranian population. J Gastrointest Cancer. 2020. https://​doi.​org/​10.​1007/​s12029-020-00438-4.
7.
Zurück zum Zitat Dastmalchi N, Khojasteh S, Nargesi MM, Safaralizadeh R. The correlation between lncRNAs and Helicobacter pylori in gastric cancer. Pathogens and disease. 2019;77(9):ftaa004.CrossRef Dastmalchi N, Khojasteh S, Nargesi MM, Safaralizadeh R. The correlation between lncRNAs and Helicobacter pylori in gastric cancer. Pathogens and disease. 2019;77(9):ftaa004.CrossRef
8.
Zurück zum Zitat Yang H, Chen W, Jiang G, Yang J, Wang W, Li H. Long non-coding RNA EWSAT1 contributes to the proliferation and invasion of glioma by sponging miR-152-3p. Oncol Lett. 2020;20(2):1846–54.CrossRef Yang H, Chen W, Jiang G, Yang J, Wang W, Li H. Long non-coding RNA EWSAT1 contributes to the proliferation and invasion of glioma by sponging miR-152-3p. Oncol Lett. 2020;20(2):1846–54.CrossRef
9.
Zurück zum Zitat Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661–7.CrossRef Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661–7.CrossRef
10.
Zurück zum Zitat Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRef Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.CrossRef
11.
Zurück zum Zitat Ji H, Hui B, Wang J, Zhu Y, Tang L, Peng P, et al. Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression. Cancer Sci. 2019;110(1):72–85.CrossRef Ji H, Hui B, Wang J, Zhu Y, Tang L, Peng P, et al. Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression. Cancer Sci. 2019;110(1):72–85.CrossRef
12.
Zurück zum Zitat Han W, Shi J, Cao J, Dong B, Guan W. Latest advances of long non-coding RNA SNHG5 in human cancers. Onco Targets Ther. 2020;13:6393–403.CrossRef Han W, Shi J, Cao J, Dong B, Guan W. Latest advances of long non-coding RNA SNHG5 in human cancers. Onco Targets Ther. 2020;13:6393–403.CrossRef
13.
Zurück zum Zitat Bhan A, Soleimani M, Mandal SS. Long noncoding RNA, and cancer: a new paradigm. Cancer Res. 2017;77(15):3965–81.CrossRef Bhan A, Soleimani M, Mandal SS. Long noncoding RNA, and cancer: a new paradigm. Cancer Res. 2017;77(15):3965–81.CrossRef
14.
Zurück zum Zitat Riahi A, Hosseinpour-Feizi M, Rajabi A, Akbarzadeh M, Montazeri V, Safaralizadeh R. Overexpression of long non-coding RNA MCM3AP-AS1 in breast cancer tissues compared to adjacent non-tumour tissues. Br J Biomed Sci. 2020;7:1–5. Riahi A, Hosseinpour-Feizi M, Rajabi A, Akbarzadeh M, Montazeri V, Safaralizadeh R. Overexpression of long non-coding RNA MCM3AP-AS1 in breast cancer tissues compared to adjacent non-tumour tissues. Br J Biomed Sci. 2020;7:1–5.
15.
Zurück zum Zitat Wang Z, Liu X, Liu X, Niu D. Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A. Cancer Manag Res. 2020;12:6629–40.CrossRef Wang Z, Liu X, Liu X, Niu D. Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A. Cancer Manag Res. 2020;12:6629–40.CrossRef
16.
Zurück zum Zitat Zhao H, Zhang X, Frazão JB, Condino-Neto A, Newburger PE. HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells. J Cell Biochem. 2013;114(10):2375–83.CrossRef Zhao H, Zhang X, Frazão JB, Condino-Neto A, Newburger PE. HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells. J Cell Biochem. 2013;114(10):2375–83.CrossRef
17.
Zurück zum Zitat Song N, Zhang Y, Kong F, Yang H, Ma X. HOXA-AS2 promotes type I endometrial carcinoma via miRNA-302c-3p-mediated regulation of ZFX. Cancer Cell Int. 2020;20:359.CrossRef Song N, Zhang Y, Kong F, Yang H, Ma X. HOXA-AS2 promotes type I endometrial carcinoma via miRNA-302c-3p-mediated regulation of ZFX. Cancer Cell Int. 2020;20:359.CrossRef
18.
Zurück zum Zitat Herrero R, Heise K, Acevedo J, Cook P, Gonzalez C, Gahona J, et al. Regional variations in Helicobacter pylori infection, gastric atrophy, and gastric cancer risk: the ENIGMA study in Chile. PLoS One. 2020;15(9):e0237515.CrossRef Herrero R, Heise K, Acevedo J, Cook P, Gonzalez C, Gahona J, et al. Regional variations in Helicobacter pylori infection, gastric atrophy, and gastric cancer risk: the ENIGMA study in Chile. PLoS One. 2020;15(9):e0237515.CrossRef
19.
Zurück zum Zitat Baj J, Korona-Głowniak I, Forma A, Maani A, Sitarz E, Rahnama-Hezavah M, et al. Mechanisms of the epithelial-mesenchymal transition and tumor microenvironment in Helicobacter pylori-induced gastric cancer. Cells. 2020;9(4):1055.CrossRef Baj J, Korona-Głowniak I, Forma A, Maani A, Sitarz E, Rahnama-Hezavah M, et al. Mechanisms of the epithelial-mesenchymal transition and tumor microenvironment in Helicobacter pylori-induced gastric cancer. Cells. 2020;9(4):1055.CrossRef
20.
Zurück zum Zitat Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998;114(6):1169–79.CrossRef Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998;114(6):1169–79.CrossRef
21.
Zurück zum Zitat Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE. Epidemiology of Helicobacter pylori and CagA-positive infections and global variations in gastric cancer. Toxins (Basel). 2018;10(4):163.CrossRef Park JY, Forman D, Waskito LA, Yamaoka Y, Crabtree JE. Epidemiology of Helicobacter pylori and CagA-positive infections and global variations in gastric cancer. Toxins (Basel). 2018;10(4):163.CrossRef
22.
Zurück zum Zitat Tan H, Zhang S, Zhang J, Zhu L, Chen Y, Yang H, et al. Long non-coding RNAs in gastric cancer: New emerging biological functions and therapeutic implications. Theranostics. 2020;10(19):8880–902.CrossRef Tan H, Zhang S, Zhang J, Zhu L, Chen Y, Yang H, et al. Long non-coding RNAs in gastric cancer: New emerging biological functions and therapeutic implications. Theranostics. 2020;10(19):8880–902.CrossRef
23.
Zurück zum Zitat Gao Y, Xie M, Guo Y, Yang Q, Hu S, Li Z. Long non-coding RNA FGD5-AS1 regulates cancer cell proliferation and chemoresistance in gastric cancer through miR-153-3p/CITED2 axis. Front Genet. 2020;11:715.CrossRef Gao Y, Xie M, Guo Y, Yang Q, Hu S, Li Z. Long non-coding RNA FGD5-AS1 regulates cancer cell proliferation and chemoresistance in gastric cancer through miR-153-3p/CITED2 axis. Front Genet. 2020;11:715.CrossRef
24.
Zurück zum Zitat Li L, Li Y, Huang Y, Ouyang Y, Zhu Y, Wang Y, et al. Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4. Cancer Sci. 2018;109(12):3714–25.CrossRef Li L, Li Y, Huang Y, Ouyang Y, Zhu Y, Wang Y, et al. Long non-coding RNA MIF-AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4. Cancer Sci. 2018;109(12):3714–25.CrossRef
25.
Zurück zum Zitat Ding X, Zhu L, Ji T, Zhang X, Wang F, Gan S, et al. Long intergenic non-coding RNAs (LincRNAs) identified by RNA-seq in breast cancer. PLoS One. 2014;9(8):e103270.CrossRef Ding X, Zhu L, Ji T, Zhang X, Wang F, Gan S, et al. Long intergenic non-coding RNAs (LincRNAs) identified by RNA-seq in breast cancer. PLoS One. 2014;9(8):e103270.CrossRef
26.
Zurück zum Zitat Gyvyte U, Kupcinskas J, Juzenas S, Inciuraite R, Poskiene L, Salteniene V, et al. Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs). PLoS One. 2018;13(12):e0209342.CrossRef Gyvyte U, Kupcinskas J, Juzenas S, Inciuraite R, Poskiene L, Salteniene V, et al. Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs). PLoS One. 2018;13(12):e0209342.CrossRef
27.
Zurück zum Zitat Shi YB, Liu SL, Mou XR, Liao J, Che JP, Fei XQ, et al. Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer. Eur Rev Med Pharmacol Sci. 2020;24(3):1243–9.PubMed Shi YB, Liu SL, Mou XR, Liao J, Che JP, Fei XQ, et al. Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer. Eur Rev Med Pharmacol Sci. 2020;24(3):1243–9.PubMed
28.
Zurück zum Zitat Wang F, Wu D, Chen J, Chen S, He F, Fu H, et al. Long non-coding RNA HOXA-AS2 promotes the migration, invasion and stemness of bladder cancer via regulating miR-125b/Smad2 axis. Exp Cell Res. 2019;375(1):1–10.CrossRef Wang F, Wu D, Chen J, Chen S, He F, Fu H, et al. Long non-coding RNA HOXA-AS2 promotes the migration, invasion and stemness of bladder cancer via regulating miR-125b/Smad2 axis. Exp Cell Res. 2019;375(1):1–10.CrossRef
29.
Zurück zum Zitat Xiao S, Song B. LncRNA HOXA-AS2 promotes the progression of prostate cancer via targeting miR-509-3p/PBX3 axis. Biosci Rep. 2020;40(8):BSR20193287.CrossRef Xiao S, Song B. LncRNA HOXA-AS2 promotes the progression of prostate cancer via targeting miR-509-3p/PBX3 axis. Biosci Rep. 2020;40(8):BSR20193287.CrossRef
30.
Zurück zum Zitat Ding J, Xie M, Lian Y, Zhu Y, Peng P, Wang J, et al. Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer. Oncogenesis. 2017;6(1):e288.CrossRef Ding J, Xie M, Lian Y, Zhu Y, Peng P, Wang J, et al. Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer. Oncogenesis. 2017;6(1):e288.CrossRef
31.
Zurück zum Zitat Xie M, Sun M, Zhu YN, Xia R, Liu YW, Ding J, et al. Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression. Oncotarget. 2015;6(32):33587–601.CrossRef Xie M, Sun M, Zhu YN, Xia R, Liu YW, Ding J, et al. Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression. Oncotarget. 2015;6(32):33587–601.CrossRef
Metadaten
Titel
Overexpression of HOXA-AS2 LncRNA in Patients with Gastric Cancer and Its Association with Helicobacter pylori Infection
verfasst von
Ali Rajabi
Atousa Riahi
Hanie Shirabadi-Arani
Yaghoub Moaddab
Mehdi Haghi
Reza Safaralizadeh
Publikationsdatum
10.11.2020
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1/2022
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-020-00549-y

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