Volume 25, Issue 3 (5-2021)                   IBJ 2021, 25(3): 157-168 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mahmoudian R A, Lotfi Gharaie M, Abbaszadegan R, Forghanifard M M, Abbaszadegan M R. Interaction between LINC-ROR and Stemness State in Gastric Cancer Cells with Helicobacter pylori Infection. IBJ 2021; 25 (3) :157-168
URL: http://ibj.pasteur.ac.ir/article-1-3179-en.html
Background: Large intergenic non-coding RNA regulator of reprogramming (LINC-ROR), as a cancer-related Long non-coding RNA, has vital roles in stem cell survival, pluripotency, differentiation, and self-renewal in human embryonic stem cell. However, cancer-related molecular mech­anisms, its functional roles, and clinical value of LINC-ROR in gastric cancer (GC) remain unclear. In this study, we aimed to investigate probable interplay between LINC-ROR with SALL4 stemness regulator and their role with the development of the disease. Methods: The mRNA expression profile of LINC-ROR and SALL4 was assessed in tumoral and adjacent non-cancerous tissues of GC patients, using quantitative real-time PCR. Results: Significant LINC-ROR underexpression and SALL4 overexpression were observed in 55.81% and 75.58% (p < 0.0001) of samples, respectively. The expression of LINC-ROR and SALL4 were significantly correlated with each other (p = 0.044). There was an association between the underexpression of LINC-ROR and sex, stage of tumor progression, tumor type, and location of tumor (p < 0.05), and Helicobacter pylori infection with SALL4 expression (p = 0.036). There were also significant correlations between concomitant mRNA expression of SALL4 and LINC-ROR in tumors located at distal noncardiac, positive for H. pylori infection, tumors with invasion into the muscle layer of the stomach, and grade II tumor (p < 0.05). Conclusion: The clinical results of the SALL4-LINC-ROR association propose a probable functional interaction between these markers in tumor maintenance and aggressiveness. Our study can help to understand one of the mechanisms involved in the progression of gastric cancer through the function of these regulators.
Type of Study: Full Length/Original Article | Subject: Cancer Biology

1. FU DG. Epigenetic alterations in gastric cancer. Molecular medicine reports 2015; 12(3): 3223-3230. [DOI:10.3892/mmr.2015.3816]
2. Yamashita S, Kishino T, Takahashi T, Shimazu T, Charvat H, Kakuqawa R, Nakajima T, Lee YC, Lida N, Maeda M, Hattori N, Takeshima H, Nagano R, Oda Ichiro Tsugane S, Shiang M, Ushijirna T. Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues. Proceedings of the national academy of sciences 2018; 115(6): 1328-1333. [DOI:10.1073/pnas.1717340115]
3. Tamura G. Genetic and epigenetic alterations of tumor suppressor and tumor-related genes in gastric cancer. Histology and histopathology 2002; 17(1): 323-329.
4. Patel TN, S Roy, and R Ravi. Gastric cancer and related epigenetic alterations. Ecancermedicalscience 2017; 11: 714. [DOI:10.3332/ecancer.2017.714]
5. Zhou Z, Lin Z, Pang X, Tariq MA, Ao X, Li P, Wang J. Epigenetic regulation of long non-coding RNAs in gastric cancer. Oncotarget 2018; 9(27): 19443-19458. [DOI:10.18632/oncotarget.23821]
6. Chao-Po L, He L. Noncoding RNAs in cancer development. Annual review of cancer biology 2017; 1: 163-184. [DOI:10.1146/annurev-cancerbio-050216-034443]
7. Chen J, Wang R, Zhang K, Chen LB. Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets. Journal of cellular and molecular medicine 2014; 18(12): 2425-2436. [DOI:10.1111/jcmm.12431]
8. Cheetham S, Gruhi F, Matick JS, Dinger ME. Long noncoding RNAs and the genetics of cancer. British journal of cancer 2013; 108(12): 2419-2425. [DOI:10.1038/bjc.2013.233]
9. Han W, Xiao R, Zhang C, Suyila Q, Li X, Su X. Selecting lncRNAs in gastric cancer cells for directed therapy with bioactive peptides and chemotherapy drugs. Oncotarget 2017; 8(49): 86082-86097. [DOI:10.18632/oncotarget.20977]
10. Lin MT, Song HJ, Ding XY. Long non-coding RNAs involved in metastasis of gastric cancer. World journal of gastroenterology 2018; 24(33): 3724-3737. [DOI:10.3748/wjg.v24.i33.3724]
11. Li T, Mo X, Fu L, Xiao B, Guo J. Molecular mechanisms of long noncoding RNAs on gastric cancer. Oncotarget 2016; 7(8): 8601-8612. [DOI:10.18632/oncotarget.6926]
12. Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: New links in cancer progression. Cancer research 2011; 71(1): 3-7. [DOI:10.1158/0008-5472.CAN-10-2483]
13. Cabili MN, Trapnell C, Goff L, Koziol M, Vega BT, Regev A, Rinn J. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes and development 2011; 25(18): 1915-1927. [DOI:10.1101/gad.17446611]
14. Wang Y, Xu z, Jiang J, Jiuhon C, Leixiao GK, Wu M, Xiong J, Guo X, Liu H. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Developmental cell 2013; 25(1): 69-80. [DOI:10.1016/j.devcel.2013.03.002]
15. Pan Y, Li Chen, Zhang K, Chu X, Wang R, Chen L.The emerging roles of long noncoding RNA ROR (lincRNA-ROR) and its possible mechanisms in human cancers. Cellular physiology and biochemistry 2016; 40(1-2): 219-229. [DOI:10.1159/000452539]
16. Lu R, Chen J, Kong L, Zhu H. Prognostic value of lncRNA ROR expression in various cancers: A meta-analysis. Bioscience reports 2018; 38(5): 20181095. [DOI:10.1042/BSR20181095]
17. Fico A, Fiorenzano A, Pascale E, Patriarca EJ, Minchiotti G. Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation. Cellular and molecular life sciences 2019; 76(8): 1459-1471. [DOI:10.1007/s00018-018-3000-z]
18. Zhang J, Tam WL, Tong GQ, Wu Q, Yun chan H, SEnsoh B,LOu Y, Yang J, Ma Y, Chai Li, Hui Ng H, Lufkin T, Robson P, Lim B. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nature cell biology 2006; 8(10): 1114-1123. [DOI:10.1038/ncb1481]
19. Pan L, Liang W, Gu J, Zang X, Huang Z, Shi H, Chen J, Fu M, Zhang P, Xiao X, Qian H, Xu W, Jiang P, Zhang X. Long noncoding RNA DANCR is activated by SALL4 and promotes the proliferation and invasion of gastric cancer cells. Oncotarget 2018; 9(2): 1915-1930. [DOI:10.18632/oncotarget.23019]
20. Viiri LE, Rantapero T, Kiamehr M, Alexanova A, Oittinen M, Viiri K, Niskanen H, Nykter M, Kaikkonen MU, Aalto-Setala K. Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation. Scientific reports 2019; 9(1): 3562. [DOI:10.1038/s41598-019-39215-0]
21. Forghanifard MM, Khales SA, Mallak A, Farshchian M, Abbaszadegan MR. Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Medical oncology 2014; 31(4): 922. [DOI:10.1007/s12032-014-0922-7]
22. Yuan X, Zhang X, Zhang W, Liang W, Zhang P, Shi H, Zhang B, Shao M, Yam Y, Qian H, Xu W. SALL4 promotes gastric cancer progression through activating CD44 expression. Oncogenesis 2016; 5(11): e268. [DOI:10.1038/oncsis.2016.69]
23. Dirican E, Akkiprik M. Functional and clinical significance of SALL4 in breast cancer. Tumor biology 2016; 37(9): 11701-11709. [DOI:10.1007/s13277-016-5150-7]
24. Kobayashi D, Kuribayashi K, Tanaka M. Watanabe N. Overexpression of SALL4 in lung cancer and its importance in cell proliferation. Oncology reports 2011; 26(4): 965-970.
25. Khales SA, Abbaszadegan MR, Abdollahi A, Raeisossadati R, Tousi F, Forghanifard MM. SALL4 as a new biomarker for early colorectal cancers. Journal of cancer research and clinical oncology 2015; 141(2): 229-235. [DOI:10.1007/s00432-014-1808-y]
26. Sahebi R, Malakootian M, Balalaee B, Shahrvari A, Khoshnia M, Abbaszadehgan MR, Moradi A, Mowta SJ. Linc-ROR and its spliced variants 2 and 4 are significantly up-regulated in esophageal squamous cell carcinoma. Iranian journal of basic medical sciences 2016; 19(10): 1131-1135.
27. Xia F, Xiong Y, Li Q. Interaction of lincRNA ROR and p53/miR-145 correlates with lung cancer stem cell signatures. Journal of cellular biochemistry 2017; DOI: 10.1002/jcb.25960. [DOI:10.1002/jcb.25960]
28. Chen Y, Peng Ya, Xu Z, Ge Bo, Xiang X, Zhang T, Gao Li , shi H, Wang C, Huang J. LncROR promotes bladder cancer cell proliferation, migration, and epithelial-mesenchymal transition. Cellular physiology and biochemistry 2017; 41(6): 2399-2410. [DOI:10.1159/000475910]
29. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Yumours. 7th edition. UK: John Wiley & Sons; 2011.
30. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Noian T, Wpfaffi MW, Shipley GL, Vandesompele J, Wittwer CT.The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments. Clinical chemistry 2009; 55(4): 611-622. [DOI:10.1373/clinchem.2008.112797]
31. Zou Z, Ding Q, Li P, Cao R, Shi L, Feng Y, Peng G. Overexpression of lincRNA-ROR predicts poor prognosis in patients with gastric cancer. International journal of clinical and experimental pathology 2016; 9(9): 9467-9472.
32. Barooei R, Mahmoudian RA, Abbaszadegan MR, Mansouri A, Gholamin M. Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer. Medical oncology 2015; 32(8): 217. [DOI:10.1007/s12032-015-0653-4]
33. Rivas-Ortiz CI, Vidal YL, Arrendondo Hernandez LR, Rojas GC. Genetic alterations in gastric cancer associated with Helicobacter pylori infection. Frontiers in medicine 2017; 4: 47. [DOI:10.3389/fmed.2017.00047]
34. Veisani Y, Delpisheh A. Survival rate of gastric cancer in Iran; a systematic review and meta-analysis. Gastroenterology and hepatology from bed to bench 2016; 9(2): 78-86.
35. Raju KL, Augustine D, Rao RS, SVS, Haragannavar VC, Nambiar S, Prasad K, Awan KH, Patil S. Biomarkers in tumorigenesis using cancer cell lines: A systematic review. Asian Pacific journal of cancer prevention 2017; 18(9): 2329-2337.
36. Feng S, Yao J, Chen Y, Geng P, Zhang H, Ma X, Zhao J, Yu X. Expression and functional role of reprogramming-related long noncoding RNA (lincRNA-ROR) in glioma. Journal of molecular neuroscience 2015; 56(3): 623-630. [DOI:10.1007/s12031-014-0488-z]
37. Gyvyte U, Kupcinskas J, Juzenas S, Inciuraite R, Poskiene L,Salteniene V, Link A, Fassan M, Franke A, Kupcinskas L, Skieceviciene J. Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs). PloS one 2018; 13(12): e0209342. [DOI:10.1371/journal.pone.0209342]
38. Luo C, Cao J, Peng R, Guo Q, Ye H, Wang P, Wang K, Song C. Functional variants in linc-ROR are associated with mRNA expression of LINC-ROR and breast cancer susceptibility. Scientific reports 2018; 8(1): 4680. [DOI:10.1038/s41598-018-22881-x]
39. Wang S, Liu F, Deng J, Cai X, Han J, Liu Qi. Long noncoding RNA ROR regulates proliferation, invasion, and stemness of gastric cancer stem cell. Cellular reprogramming 2016; 18(5): 319-326. [DOI:10.1089/cell.2016.0001]
40. Rezaei M, Emadi-Baygi M, Hoffmann MJ, Schulz WA, Nikpour P. Altered expression of LINC-ROR in cancer cell lines and tissues. Tumor biology 2016; 37(2): 1763-1769. [DOI:10.1007/s13277-015-3933-x]
41. Hiyama T, Tanaka S, Yoshihara M, Sasao S, Kose K, Shima H, Tuncel H, Ueno Y, Ito M, Kitadai Y, Yasui W, Haruma K , Chayama K. Chromosomal and microsatellite instability in sporadic gastric cancer. Journal of gastroenterology and hepatology 2004; 19(7): 756-760. [DOI:10.1111/j.1440-1746.2004.03369.x]
42. Toraih EA, El-Wazir A, Hussein MH, Khashana MS, Matter A, Fawzy MS, Hosny S. Expression of long intergenic non-coding RNA, regulator of reprogramming, and its prognostic value in patients with glioblastoma. The International journal of biological markers 2019; 34(1): 69-79. [DOI:10.1177/1724600818814459]
43. Fu Z, Li Guolin , Li Zhihua, Wang Y, Zhao Y, Zheng S, Ye H, Luo Y, Zhao x, Wei L, Liu Y, Lin Q, Zhou Q, Chen R. Endogenous miRNA Sponge LincRNA-ROR promotes proliferation, invasion and stem cell-like phenotype of pancreatic cancer cells. Cell death discovery 2017; 3: 17004. [DOI:10.1038/cddiscovery.2017.4]
44. Gao S, Wang P, Hua Y, Xi H, Meng Z, Liu T, Chen Z, Liu L. ROR functions as a ceRNA to regulate Nanog expression by sponging miR-145 and predicts poor prognosis in pancreatic cancer. Oncotarget 2016; 7(2): 1608-1616. [DOI:10.18632/oncotarget.6450]
45. Hou P, Zhao y, Li z, Yao R, Ma M, Gao Y, Zhao L, Zhang Y, Huang B, Lu J. LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell death and disease 2014; 5(6): 1287. [DOI:10.1038/cddis.2014.249]
46. Hou L, Tu J, Cheng F, Yang H, Yu F, Wang M, Lu J, Fan J, Zhou G. Long noncoding RNA ROR promotes breast cancer by regulating the TGF-β pathway. Cancer cell international 2018; 18(1): 142. [DOI:10.1186/s12935-018-0638-4]
47. Liu X, L Cui, and J Liu. Increased lincRNA ROR is association with poor prognosis for esophageal squamous cell carcinoma patients. Intertional journal of clinical experimental pathology 2017; 10: 4654-4660.
48. Takahashi K, Irene K, Haga H, Patel T. Modulation of hypoxia-signaling pathways by extracellular linc-RoR. Journal of cell science 2014; 127(Pt7): 1585-1594. [DOI:10.1242/jcs.141069]
49. Arunkumar G, Arunagiri KD, Magendhra Rao, Mayakannan M, Kanagaraj A, Vilvanathan V , Sundaramoorthy R , Kottayasamy SR , Ramamurthy R , Arasambattu KM. Expression profiling of long non-
50. coding RNA identifies linc-RoR as a prognostic biomarker in oral cancer. Tumor biology 2017; 39(4): 1010428317698366.
51. Zhou X, Gao Q, Wang J, Zhang X, Liu K, Duan Z. Linc-RNA-RoR acts as a "sponge" against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecologic oncology 2014; 133(2): 333-339. [DOI:10.1016/j.ygyno.2014.02.033]
52. Cheng, EC, Lin H. Repressing the repressor: a lincRNA as a MicroRNA sponge in embryonic stem cell self-renewal. Developmental cell 2013; 25(1): 1-2. [DOI:10.1016/j.devcel.2013.03.020]
53. Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley G, Rinn JL. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nature genetics 2010; 42(12): 1113-1117. [DOI:10.1038/ng.710]
54. Wang L, YU L, Zhang Z, Pang L, Xu J, Jiang J, Liang W, Chai Y, Hou J, Li F. LINC-ROR promotes esophageal squamous cell carcinoma progression through the derepression of SOX9. Journal of experimental and clinical cancer research 2017; 36(1): 182. [DOI:10.1186/s13046-017-0658-2]
55. Yuan X, Zhang X, Zhang W, Liang W, Zhang P, Shi H, Zhang B, Shao M, Yan Y, Qian H, Xu W. SALL4 promotes gastric cancer progression through activating CD44 expression. Oncogenesis 2016; 5(11): e268. [DOI:10.1038/oncsis.2016.69]
56. Osman MA, Bloom GS, Tagoe EA. Helicobacter pylori‐induced alteration of epithelial cell signaling and polarity: A possible mechanism of gastric carcinoma etiology and disparity. Cytoskeleton 2013; 70(7): 349-359. [DOI:10.1002/cm.21114]
57. Zhou X, Chen H, Zhu L, Hao B, Zhang W, Hua J, Gu H, Jin W, Zhang G. Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c. Oncotarget 2016; 7(50): 82770 -82782. [DOI:10.18632/oncotarget.13165]
58. Amieva M. and RM Peek Jr. Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology 2016; 150(1): 64-78. [DOI:10.1053/j.gastro.2015.09.004]
59. Sue S, Shibata W, Maeda S. Helicobacter pylori-induced signaling pathways contribute to intestinal metaplasia and gastric carcinogenesis. Biomed research international 2015; 2015: 737621. [DOI:10.1155/2015/737621]

Add your comments about this article : Your username or Email:

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb