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Research Article

Investigating the Association between LncRNA NR2F2-AS1, miR-320b, and BMI1 in Gastric Cancer: Insights into Expression Profiles as Potential Biomarkers for Disease Management

Author(s): Shadi Ghorbanzadeh, Navid Pourghasem, Roghayeh Amiz, Masoomeh Afsa and Kianoosh Malekzadeh*

Volume 13, Issue 3, 2024

Published on: 28 June, 2024

Page: [211 - 224] Pages: 14

DOI: 10.2174/0122115366291818240606112725

Price: $65

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Abstract

Aim: This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1.

Background: Gastric cancer is a high-mortality malignancy, and understanding the underlying molecular mechanisms is crucial. Non-coding RNAs play an important role in gene expression, and their dysregulation can lead to tumor initiation and progression.

Objective: This study aims to determine the pathological role of LncRNA NR2F2-AS1 in gastric cancer progression and its association with the clinicopathological characteristics of patients.

Methods: Bioinformatics databases were used to predict the expression levels and interactions between the studied factors to achieve this objective. The expression pattern of NR2F2-AS1/miR- 320b/BMI1 in 40 pairs of tumor and adjacent normal tissues was examined using RT-PCR, IHC, and western blot. The correlation, ROC curve, and survival analyses were also conducted for the aforementioned factors.

Results: The results showed an increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1 in lower stages, and the elevation continued with the increasing stage of the disease. This correlated with significant downregulation of miR-320b and PTEN, indicating their association with gastric cancer progression and decreased patient survival. LncRNA NR2F2-AS1 acts as an oncogene by influencing the level of miR-320b, altering the amount of BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. ROC curve analysis indicated that alteration in the lncRNA NR2F2-AS1 level showed more than 98.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis.

Conclusion: In conclusion, these results suggest that NR2F2-AS1/miR-320b/BMI1 has the potential to be a prognostic as well as diagnostic biomarker for gastric cancer.

Keywords: LncRNA NR2F2-AS1, BMI1, MiR-320b, gastric cancer, expression, biomarker.

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[1]
Rijken A, Lurvink RJ, Luyer MDP, et al. The burden of peritoneal metastases from gastric cancer: A systematic review on the incidence, risk factors and survival. J Clin Med 2021; 10(21): 4882.
[http://dx.doi.org/10.3390/jcm10214882] [PMID: 34768402]
[2]
Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: Epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol 2023; 20(5): 338-49.
[http://dx.doi.org/10.1038/s41571-023-00747-0] [PMID: 36959359]
[3]
Waddingham W, Nieuwenburg SAV, Carlson S, et al. Recent advances in the detection and management of early gastric cancer and its precursors. Frontline Gastroenterol 2021; 12(4): 322-31.
[http://dx.doi.org/10.1136/flgastro-2018-101089] [PMID: 34249318]
[4]
Thrift AP, Nguyen TH. Gastric cancer epidemiology. Gastrointest Endosc Clin N Am 2021; 31(3): 425-39.
[http://dx.doi.org/10.1016/j.giec.2021.03.001] [PMID: 34053631]
[5]
Gil N, Ulitsky I. Regulation of gene expression by cis-acting long non-coding RNAs. Nat Rev Genet 2020; 21(2): 102-17.
[http://dx.doi.org/10.1038/s41576-019-0184-5] [PMID: 31729473]
[6]
Wu Q, Ma J, Wei J, Meng W, Wang Y, Shi M. lncRNA SNHG11 promotes gastric cancer progression by activating the Wnt/β-catenin pathway and oncogenic autophagy. Mol Ther 2021; 29(3): 1258-78.
[http://dx.doi.org/10.1016/j.ymthe.2020.10.011] [PMID: 33068778]
[7]
Zhang S, Zhang X, Sun Q, et al. LncRNA NR2F2‐AS1 promotes tumourigenesis through modulating BMI1 expression by targeting miR‐320b in non‐small cell lung cancer. J Cell Mol Med 2019; 23(3): 2001-11.
[http://dx.doi.org/10.1111/jcmm.14102] [PMID: 30592135]
[8]
Liu J, Qian J, Mo Q, Tang L, Xu Q. LncRNA NR2F2-AS1 silencing induces cell cycle arrest in G0/G1 phase via downregulating cyclin D1 in colorectal cancer. Cancer Manag Res 2020; 12: 1835-43.
[http://dx.doi.org/10.2147/CMAR.S221996] [PMID: 32210626]
[9]
Fu X, Wang D, Shu T, Cui D, Fu Q. LncRNA NR2F2-AS1 positively regulates CDK4 to promote cancer cell proliferation in prostate carcinoma. Aging Male 2020; 23(5): 1073-9.
[http://dx.doi.org/10.1080/13685538.2019.1670157] [PMID: 31566058]
[10]
Liu H, Zhang Z, Wu N, et al. Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals functional lncRNAs in gastric cancer. Genes (Basel) 2018; 9(6): 303.
[http://dx.doi.org/10.3390/genes9060303] [PMID: 29912172]
[11]
Jingyang Z, Jinhui C, Lu X, et al. Mir-320b inhibits pancreatic cancer cell proliferation by targeting FOXM1. Curr Pharm Biotechnol 2021; 22(8): 1106-13.
[http://dx.doi.org/10.2174/18734316MTEwsMDIDy] [PMID: 32942974]
[12]
Wu K, Wang X, Yu H, Yu Z, Wang D, Xu X. LINC00460 facilitated tongue squamous cell carcinoma progression via the miR‐320b/IGF2BP3 axis. Oral Dis 2022; 28(6): 1496-508.
[http://dx.doi.org/10.1111/odi.13828] [PMID: 33660359]
[13]
Zhu S, Zhao D, Li C, et al. BMI1 is directly regulated by androgen receptor to promote castration-resistance in prostate cancer. Oncogene 2020; 39(1): 17-29.
[http://dx.doi.org/10.1038/s41388-019-0966-4] [PMID: 31462713]
[14]
Liu J, Jiang Y, Huang H, et al. BMI ‐1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes. Cancer Sci 2023; 114(2): 449-62.
[http://dx.doi.org/10.1111/cas.15623] [PMID: 36285479]
[15]
Chen MK, Zhou JH, Wang P, et al. BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell. Aging (Albany NY) 2021; 13(14): 18310-30.
[http://dx.doi.org/10.18632/aging.203277] [PMID: 34270461]
[16]
Selmin OI, Donovan MG, Stillwater BJ, Neumayer L, Romagnolo DF. Epigenetic regulation and dietary control of triple negative breast cancer. Front Nutr 2020; 7: 159.
[http://dx.doi.org/10.3389/fnut.2020.00159] [PMID: 33015128]
[17]
Xu J, Li L, Shi P, Cui H, Yang L. The crucial roles of Bmi-1 in cancer: Implications in pathogenesis, metastasis, drug resistance, and targeted therapies. Int J Mol Sci 2022; 23(15): 8231.
[http://dx.doi.org/10.3390/ijms23158231] [PMID: 35897796]
[18]
Yura M, Yoshikawa T, Otsuki S, et al. Is surgery alone sufficient for treating T1 gastric cancer with extensive lymph node metastases? Gastric Cancer 2020; 23(2): 349-55.
[http://dx.doi.org/10.1007/s10120-019-01006-x] [PMID: 31512081]
[19]
Torres OP, Cucho SP, Rojas LT. Clinicopathological factors associated with the presence of tumor deposits in resected gastric cancer patients. Heliyon 2021; 7(6)
[PMID: 34307933]
[20]
Biswas K, Janani G, Udayakumar S, Deepika B, Girigoswami K. Rough edges of reduced graphene oxide (rGO) sheets elicit anticancerous activities: An in vitro study. Results Chem 2023; 6: 101207.
[http://dx.doi.org/10.1016/j.rechem.2023.101207]
[21]
Girigoswami K, Pallavi P, Girigoswami A. Targeting cancer stem cells by nanoenabled drug deliveryCancer Stem Cells: New Horizons in Cancer Therapies. Berlin, Heidelberg: SpringerLink 2020.
[http://dx.doi.org/10.1007/978-981-15-5120-8_17]
[22]
Liu Y, Ao X, Wang Y, Li X, Wang J. Long non-coding RNA in gastric cancer: Mechanisms and clinical implications for drug resistance. Front Oncol 2022; 12: 841411.
[http://dx.doi.org/10.3389/fonc.2022.841411] [PMID: 35155266]
[23]
Girigoswami K, Girigoswami A. A review on the role of nanosensors in detecting cellular miRNA expression in colorectal cancer. Endocr Metab Immune Disord Drug Targets 2021; 21(1): 12-26.
[http://dx.doi.org/10.2174/1871530320666200515115723]
[24]
Li F, Jiang Z, Shao X, Zou N. Downregulation of lncRNA NR2F2 antisense RNA 1 induces G1 arrest of colorectal cancer cells by downregulating cyclin-dependent kinase 6. Dig Dis Sci 2020; 65(2): 464-9.
[http://dx.doi.org/10.1007/s10620-019-05782-5] [PMID: 31432342]
[25]
Qin H, Qin C. Downregulation of long non-coding RNA NR2F2-AS1 inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cells by upregulating the expression of PTEN. Oncol Lett 2020; 19(2): 1145-50.
[PMID: 31966043]
[26]
Liu D, Huang K, Wang T, et al. NR2F2-AS1 accelerates cell proliferation through regulating miR-4429/MBD1 axis in cervical cancer. Biosci Rep 2020; 40(6): BSR20194282.
[http://dx.doi.org/10.1042/BSR20194282] [PMID: 32469064]
[27]
Xia B, Hou L, Kang H, et al. NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells. BMC Cancer 2020; 20(1): 626.
[http://dx.doi.org/10.1186/s12885-020-07107-6] [PMID: 32631390]
[28]
Mauri F, Schepkens C, Lapouge G. NR2F2 controls malignant squamous cell carcinoma state by promoting stemness and invasion and repressing differentiation. Nat Cancer 2021; 2(11): 1152-69.
[http://dx.doi.org/10.1038/s43018-021-00287-5]
[29]
Baribault C, Ehrlich KC, Ponnaluri VKC, Pradhan S, Lacey M, Ehrlich M. Developmentally linked human DNA hypermethylation is associated with down-modulation, repression, and upregulation of transcription. Epigenetics 2018; 13(3): 275-89.
[http://dx.doi.org/10.1080/15592294.2018.1445900] [PMID: 29498561]
[30]
Liu C, Li Q-G, Zhou Y, et al. LncRNA NR2F2-AS1 induces epithelial-mesenchymal transition of non-small cell lung cancer by modulating BVR/ATF-2 pathway via regulating miR-545-5p/c-Met axis. Am J Cancer Res 2021; 11(10): 4844-65.
[PMID: 34765296]
[31]
Jiang ZY, Ma XM, Luan XH, et al. BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells. World J Gastroenterol 2023; 29(23): 3606-21.
[http://dx.doi.org/10.3748/wjg.v29.i23.3606] [PMID: 37398890]
[32]
Wu K, Woo SM, Seo SU, Kwon TK. Inhibition of BMI-1 induces apoptosis through downregulation of DUB3-Mediated Mcl-1 stabilization. Int J Mol Sci 2021; 22(18): 10107.
[http://dx.doi.org/10.3390/ijms221810107] [PMID: 34576269]
[33]
Liu Y, Xu J, Jiang M, Ni L, Ling Y. CircRNA DONSON contributes to cisplatin resistance in gastric cancer cells by regulating miR-802/BMI1 axis. Cancer Cell Int 2020; 20(1): 261.
[http://dx.doi.org/10.1186/s12935-020-01358-w] [PMID: 32581651]
[34]
Wu Z, Ding Z, Cheng B, Cui Z. The inhibitory effect of human DEFA5 in growth of gastric cancer by targeting BMI1. Cancer Sci 2021; 112(3): 1075-83.
[http://dx.doi.org/10.1111/cas.14827] [PMID: 33503272]
[35]
Moghaddam M, Vivarelli S, Falzone L, Libra M, Bonavida B. Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: Therapeutic implications. Expl Targ Anti-tumor Ther 2023; 4(2): 170-207.
[http://dx.doi.org/10.37349/etat.2023.00128] [PMID: 37205308]
[36]
Wang Q, Mao X, Luo F, Wang J. LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway. J Cell Mol Med 2021; 25(19): 9112-27.
[http://dx.doi.org/10.1111/jcmm.16656] [PMID: 34427967]

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