lncRNA MALAT1, MEG3, and PANDAR Levels may be Potential Diagnostic Biomarkers in Multiple Myeloma

Year 2023, Volume: 5 Issue: 3, 587 - 93, 18.09.2023

Elvin Eröksüz Özdinç , Kuyaş Hekimler Öztürk , Fadime Mutlu İçduygu , Demircan Özbalcı

https://doi.org/10.37990/medr.1309886

Abstract

Aim: Long non-coding RNAs (lncRNAs) play a significant role in the development of various diseases, including cancer, and have been investigated as potential diagnostic and prognostic markers. The specific mechanisms underlying their involvement in the progression and development of multiple myeloma (MM), as well as their potential as diagnostic markers, remain to be fully elucidated. This study aimed to elucidate the involvement of lncRNAs in the pathogenesis of MM, explore their relationship with clinical parameters, and assess their potential as biomarkers for MM diagnosis.
Material and Methods: Patients above 18 years of age, diagnosed with MM and not yet receiving treatment, were included in the study. The expression levels of three lncRNAs (MALAT1, PANDAR, MEG3) regulated by the p53 gene were determined in a study involving 19 patients diagnosed with MM and 20 healthy volunteers. The expression levels were determined using RT-PCR.
Results: The levels of plasma lncRNAs were observed to be significantly down-regulated (p<0.05) in the patient group. No significant difference was observed between disease stages and the expression levels of the lncRNAs. There was a negative correlation between lncRNA expression levels and albumin levels (p=0.019; p=0.048; p=0.033, respectively), while no significant associations were found with other clinicopathological characteristics. ROC analysis demonstrated that the plasma expression levels of lncRNAs had diagnostic value in predicting MM (AUC=0.729, p=0.015; AUC=0.742, p=0.010; AUC=0.703, p=0.031, respectively).
Conclusion: In conclusion, MALAT1, PANDAR and MEG3 may serve as novel biomarkers for MM patients. Furthermore, these lncRNAs may be potential drug targets in MM.

Keywords

Long non-coding RNA , multiple myeloma , MALAT1 , MEG3 , PANDAR

References

• 1. Dong H, Jiang S, Fu Y, et al. Upregulation of lncRNA NR_046683 serves as a prognostic biomarker and potential drug target for multiple myeloma. Front Pharmacol. 2019;10:45.
• 2. Cho SF, Chang YC, Chang CS, et al. MALAT1 long non-coding RNA is overexpressed in multiple myeloma and may serve as a marker to predict disease progression. BMC Cancer. 2014;14:809.
• 3. Cui YS, Song YP, Fang BJ. The role of long non-coding RNAs in multiple myeloma. Eur J Haematol. 2019;103:3-9.
• 4. Hauptman N, Glavač D. Long non-coding RNA in cancer. Int J Mol Sci. 2013;14:4655-69.
• 5. Xu TP, Huang MD, Xia R, et al. Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectin1 expression. J Hematol Oncol. 2014;7:63.
• 6. Liu J, Ben Q, Lu E, et al. Long noncoding RNA PANDAR blocks CDKN1A gene transcription by competitive interaction with p53 protein in gastric cancer. Cell Death Dis. 2018;9:168.
• 7. Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031-41.
• 8. Chaleshi V, Irani S, Alebouyeh M, et al. Association of lncRNA-p53 regulatory network (lincRNA-p21, lincRNA-ROR and MALAT1) and p53 with the clinicopathological features of colorectal primary lesions and tumors. Oncol Lett. 2020;19:3937-49.
• 9. Goyal B, Yadav SRM, Awasthee N, et al. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875:188502.
• 10. Tripathi V, Shen Z, Chakraborty A, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 2013;9:e1003368.
• 11. Wu C, Macleod I, Su AI. BioGPS and MyGene.info: organizing online, gene-centric information. Nucleic Acids Res. 2013;41:D561-5.
• 12. Tian L, Chen X, Lun L, et al. LncRNA PANDAR is a novel prognostic biomarker in patients with cancer: a meta-analysis. Clin Lab. 2019;65. doi: 10.7754/Clin.Lab.2018.180622.
• 13. Wang Y, Zhang M, Xu H, et al. Discovery and validation of the tumor-suppressive function of long noncoding RNA PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK signaling pathway. Oncotarget. 2017;8:72182-96.
• 14. Hung T, Wang Y, Lin MF, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43:621-9.
• 15. Han L, Zhang EB, Yin DD, et al. Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2. Cell Death Dis. 2015;6:e1665.
• 16. Li X, Wang F, Sun Y, et al. Expression of long non-coding RNA PANDAR and its prognostic value in colorectal cancer patients. Int J Biol Markers. 2017;32:e218-23.
• 17. Lu M, Liu Z, Li B, et al. The high expression of long non-coding RNA PANDAR indicates a poor prognosis for colorectal cancer and promotes metastasis by EMT pathway. J Cancer Res Clin Oncol. 2017;143:71-81.
• 18. Ma P, Xu T, Huang M, Shu Y. Increased expression of LncRNA PANDAR predicts a poor prognosis in gastric cancer. Biomed Pharmacother. 2016;78:172-6.
• 19. Peng W, Fan H. Long non-coding RNA PANDAR correlates with poor prognosis and promotes tumorigenesis in hepatocellular carcinoma. Biomed Pharmacother. 2015;72:113-8.
• 20. Xu Y, Tong Y, Zhu J, Lei Z, et al. An increase in long non-coding RNA PANDAR is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer. 2017;17:373.
• 21. Meng H, Han L, Hong C, et al. Aberrant lncRNA expression in multiple myeloma. Oncol Res. 2018;26:809-16.
• 22. Ghafouri-Fard S, Taheri M. Maternally expressed gene 3 (MEG3): a tumor suppressor long non coding RNA. Biomed Pharmacother. 2019;118:109129.
• 23. Zhou Y, Zhong Y, Wang Y, et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 2007;282:24731-42.
• 24. Balik V, Srovnal J, Sulla I, et al. MEG3: a novel long noncoding potentially tumour-suppressing RNA in meningiomas. J Neurooncol. 2013;112:1-8.
• 25. Zhang X, Rice K, Wang Y, et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology. 2010;151:939-47.
• 26. Yin Q, Shen X, Cui X, Ju S. Elevated serum lncRNA TUG1 levels are a potential diagnostic biomarker of multiple myeloma. Exp Hematol. 2019;79:47-55.e2.
• 27. Huang JL, Liu W, Tian LH, et al. Upregulation of long non-coding RNA MALAT-1 confers poor prognosis and influences cell proliferation and apoptosis in acute monocytic leukemia. Oncol Rep. 2017;38:1353-62.
• 28. Schmidt LH, Spieker T, Koschmieder S, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol. 2011;6:1984-92.
• 29. Isin M, Ozgur E, Cetin G, et al. Investigation of circulating lncRNAs in B-cell neoplasms. Clin Chim Acta. 2014;431:255-9.
• 30. Yang L, Zhou JD, Zhang TJ, et al. Overexpression of lncRNA PANDAR predicts adverse prognosis in acute myeloid leukemia. Cancer Manag Res. 2018;10:4999-5007.
• 31. Sun KX, Wu DD, Chen S, et al. LncRNA MEG3 inhibit endometrial carcinoma tumorigenesis and progression through PI3K pathway. Apoptosis. 2017;22:1543-52.
• 32. Yao H, Sun P, Duan M, et al. microRNA-22 can regulate expression of the long non-coding RNA MEG3 in acute myeloid leukemia. Oncotarget. 2017;8:65211-7.
• 33. Cui X, Jing X, Long C, et al. Long noncoding RNA MEG3, a potential novel biomarker to predict the clinical outcome of cancer patients: a meta-analysis. Oncotarget. 2017;8:19049-56.
• 34. Kong H, Wu Y, Zhu M, et al. Long non-coding RNAs: novel prognostic biomarkers for liver metastases in patients with early stage colorectal cancer. Oncotarget. 2016;7:50428-36.
• 35. Wan S, Zhao H. Analysis of diagnostic and prognostic value of lncRNA MEG3 in cervical cancer. Oncol Lett. 2020;20:183.
• 36. Jiang M, Wang Q, Yu G, et al. Clinical significance of long noncoding RNA maternally expressed gene 3 in acute promyelocytic leukemia. Int J Lab Hematol. 2021;43:693-8.
• 37. Li Y, Ren H. High plasma long non-coding RNA MALAT1 expression predicts a poor prognosis of cervical cancer. Int J Clin Exp Pathol. 2017;10:4595-602.
• 38. Xia H, Chen Q, Chen Y, et al. The lncRNA MALAT1 is a novel biomarker for gastric cancer metastasis. Oncotarget. 2016;7:56209-18.
• 39. Yang Z, Sun Y, Liu R, et al. Plasma long noncoding RNAs PANDAR, FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer. Cancer Manag Res. 2019;11:6175-84.