LONG NON-CODING RNAs (lncRNAs) AND THEIR MODES OF ACTION IN LIFE: NEW APPROACHES

Abstract

Objective: When the base pairs that make up human DNA were revealed with the Human Genome Project, it was determined that only 2-3% of the genome was translated into mRNA, and 10-18% encoded RNAs that helped protein synthesis. The remaining approximately 80-87% of the genome was called ‘Junk DNA’. Later, in studies conducted on this region called junk, RNAs that do not code for protein but are involved in post-transcriptional gene regulation were discovered. Non-coding RNAs (ncRNAs) have many functions, from catalysis of biological reactions to cellular defense, from developmental processes to cellular response. Studies have shown that long non-coding RNAs (lncRNAs) have key roles in the control of gene expression and cellular processes suchas development and differentiation. Studies have shown that disorders in lncRNAs play a role in the pathogenesis of many diseases such as cancers, neurodegenerative diseases, mitochondrial diseases, immunodeficiency diseases and cardiovascular diseases. According to studies, lncRNAs are seen as promising in drug development and design approaches with their capacity to be both therapeutic targets and biomarkers in new treatment approaches. lncRNAs are also thought to serve important functions in plant immunity and response to changes in the environment. Some lncRNAs have been shown to play a role in the control of tissue differentiation and development in plants, signal transduction, and responses to environmental factors such as abiotic and biotic stress.

Result and Discussion: In this review, recent advances in the understanding of the regulatory functions of long non-coding RNAs on the biology of living organisms are discussed.

 

Keywords

• Abiotic stress
• cancer
• drug
• epigenetics
• lncRNA
• RNA
• transcription

UZUN KODLAMAYAN RNA’LAR (lncRNA’LAR) VE CANLILARDAKİ ETKİ BİÇİMLERİ: YENİ YAKLAŞIMLAR

Abstract

Amaç: İnsan Genom Projesi ile insan DNA’sını oluşturan baz çiftleri ortaya çıkartıldığında, genomun sadece %2-3’lük kısmının mRNA’ya çevrildiği, %10-18’lik kısmının ise protein sentezine yardımcı RNA’ları kodladığı belirlenmiştir. Genomun geriye kalan yaklaşık %80-87’lik kısmı ise ‘Çöp DNA’ olarak adlandırılmıştır.  Daha sonraki süreçte, çöp olarak adlandırılan bu bölgeler üzerine yapılan çalışmalarda, protein kodlamayan ancak transkripsiyon sonrası gen düzenlenmesinde görev alan RNA’lar keşfedilmiştir. Kodlamayan RNA’lar (ncRNAs); biyolojik reaksiyonların katalizlenmesinden hücresel savunmaya, gelişimsel süreçlerden hücresel cevaba kadar pek çok göreve sahiptir. Çalışmalar uzun kodlamayan RNA (long non-coding RNA, lncRNA)’ların gen ekspresyonunun kontrolünde, gelişim ve farklılaşma gibi hücresel süreçlerde anahtar rollere sahip olduklarını göstermiştir. lncRNA’larda meydana gelen bozuklukların; kanserler, nörodejeneratif hastalıklar, mitokondriyal hastalıklar, immün yetmezlik hastalıkları ve kardiyovasküler hastalıklar gibi birçok hastalığın patogenezinde rol oynadığı yapılan çalışmalarda görülmüştür. Gerçekleştirilen çalışmalara göre lncRNA’lar, yeni tedavi yaklaşımlarında hem terapötik hedef hem de biyobelirteç olabilme kapasiteleri ile ilaç geliştirme ve tasarlama yaklaşımında umut verici olarak görülmektedir. lncRNA’ların bitki bağışıklığında ve çevredeki değişikliklere tepkide önemli işlevlere hizmet ettiği de düşünülmektedir. Bazı lncRNA’ların bitkilerde doku farklılaşması ve gelişiminin kontrolü, sinyal iletimi, abiyotik ve biyotik stres gibi çevresel etmenlere verilen cevaplarda rol oynadığı görülmüştür.

Sonuç ve Tartışma: Bu derlemede uzun kodlamayan RNA’ların canlı biyolojisi üzerindeki düzenleyici fonksiyonlarının anlaşılmasındaki son gelişmelere değinilmiştir. 

Keywords

• Abiyotik stres
• epigenetik
• ilaç
• kanser
• lncRNA
• RNA
• transkripsiyon

References

1. 1. Moraes, F., Góes, A. (2016). A decade of human genome project conclusion: Scientific diffusion about our genome knowledge. Biochemistry and Molecular Biology Education, 44(3), 215-223. [CrossRef]
2. 2. Richard Boland, C. (2017). Non-coding RNA: It’s not junk. Digestive Diseases and Sciences, 62, 1107-1109. [CrossRef]
3. 3. Luo, Y., Hitz, B.C., Gabdank, I., et al. (2020). New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Research, 48(D1), 882-889. [CrossRef]
4. 4. Snyder, M.P., Gingeras, T.R., Moore, J.E., et al. (2020). Perspectives on ENCODE. Nature, 583(7818), 693-698.
5. 5. Binici, N.C., Şahbudak, B. (2023). Otizm spektrum bozukluklarında epigenetik değişiklikler: Kısa kodlamayan RNA'lara genel bakış. Turkish Journal of Child & Adolescent Mental Health, 30(2), 117-122.
6. 6. Bayoğlu, B., Cengiz, M. (2017). Kalp ve damar hastalıklarında uzun kodlanmayan RNA transkriptlerinin rolleri. Bezmialem Science, 5(2), 74-79.
7. 7. Herman, A.B., Tsitsipatis, D., Gorospe, M. (2022). Integrated lncRNA function upon genomic and epigenomic regulation. Molecular Cell, 82(12), 2252-2266. [CrossRef]
8. 8. Bridges, M.C., Daulagala, A.C., Kourtidis, A. (2021). LNCcation: lncRNA localization and function. Journal of Cell Biology, 220(2), e202009045. [CrossRef]

9. 9. Lin, Y., Pan, X., Shen, H.B. (2021). lncLocator 2.0: A cell-line-specific subcellular localization predictor for long non-coding RNAs with interpretable deep learning. Bioinformatics, 37(16), 2308-2316. [CrossRef]
10. 10. Wang, W., Min, L., Qiu, X., et al. (2021). Biological function of long non-coding RNA (LncRNA) Xist. Frontiers in Cell and Developmental Biology, 9, 645647. [CrossRef]
11. 11. Shi, S.H., Jiang, J., Sun, L., et al. (2020). Dynamic regulative biomarker: Long noncoding RNA (lncRNA) in metastatic breast cancer. Clinical Laboratory, 66(9). [CrossRef]
12. 12. Hao, L., Wu, W., Xu, Y., et al. (2023). LncRNA-MALAT1: A key participant in the occurrence and development of cancer. Molecules, 28(5), 2126. [CrossRef]
13. 13. Zhao, M., Tian, R., Sun, X., et al. (2023). lncRNA MtCIR2 positively regulates plant‐freezing tolerance by modulating CBF/DREB1 gene clusters. Plant, Cell & Environment, 46(8), 2450-2469. [CrossRef]
14. 14. Wang, T., Cai, J., Sun, S., et al. (2021). A review on predicting subcellular localization of lncRNA. 13th international conference on intelligent human-machine systems and cybernetics (IHMSC), IEEE, 154-157. [CrossRef]
15. 15. Grammatikakis, I., Lal, A. (2022). Significance of lncRNA abundance to function. Mammalian Genome, 33(2), 271-280. [CrossRef]
16. 16. Aillaud, M., Schulte, L.N. (2020). Emerging roles of long noncoding RNAs in the cytoplasmic milieu. Non-coding RNA, 6(4), 44. [CrossRef]
17. 17. Godet, A.C., Roussel, E., Laugero, N., et al. (2024). Translational control by long non-coding RNAs. Biochimie, 217, 42-53. [CrossRef]
18. 18. Sharma, U., Barwal, T.S., Khandelwal, A., et al. (2021). LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3. Biochimie, 182, 99-107. [CrossRef]
19. 19. Ghafouri-Fard, S., Kamali, M.J., Abak, A., et al. (2021). LncRNA ZFAS1: Role in tumorigenesis and other diseases. Biomedicine & Pharmacotherapy, 142, 111999. [CrossRef]
20. 20. Wang, H., Chen, Y., Liu, Y., et al. (2022). The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA. Molecular Therapy-Nucleic Acids, 27, 363-374. [CrossRef]
21. 21. Weigert, N., Schweiger, A. L., Gross, J., et al. (2023). Detection of a 7SL RNA-derived small non-coding RNA using Molecular Beacons in vitro and in cells. Biological Chemistry, 404(11-12), 1123-1136. [CrossRef]
22. 22. Statello, L., Guo, C.J., Chen, L.L., et al. (2021). Gene regulation by long non-coding RNAs and its biological functions. Nature Reviews Molecular Cell Biology, 22(2), 96-118. [CrossRef]
23. 23. Sun, W., Lu, Y., Zhang, H., et al. (2022). Mitochondrial non-coding RNAs are potential mediators of mitochondrial homeostasis. Biomolecules, 12(12), 1863. [CrossRef]
24. 24. Liang, H., Liu, J., Su, et al. (2021). Mitochondrial noncoding RNAs: New wine in an old bottle. RNA Biology, 18(12), 2168-2182. [CrossRef]
25. 25. Ghafouri-Fard, S., Dashti, S., Taheri, M. (2020). The HOTTIP (HOXA transcript at the distal tip) lncRNA: Review of oncogenic roles in human. Biomedicine & Pharmacotherapy, 127, 110158. [CrossRef]
26. 26. Zhang, Y., Lu, P., Zhou, Y., et al. (2021). Inhibition of LINK-A lncRNA overcomes ibrutinib resistance in mantle cell lymphoma by regulating Akt/Bcl2 pathway. PeerJ, 9, e12571. [CrossRef]
27. 27. Kong, Y., Nie, Z., Guo, H., et al. (2020). LINK A lncRNA is upregulated in osteosarcoma and regulates migration, invasion and stemness of osteosarcoma cells. Oncology Letters, 19(4), 2832-2838. [CrossRef]
28. 28. Garratt, H., Ashburn, R., Sopić, M., et al. (2021). Long non-coding RNA regulation of epigenetics in vascular cells. Non-Coding RNA, 7(4), 62. [CrossRef]
29. 29. Wu, A., Tang, J., Dai, Y., et al. (2022). Downregulation of long noncoding RNA CRYBG3 enhances radiosensitivity in non-small cell lung cancer depending on p53 status. Radiation Research, 198(3), 297-305. [CrossRef]
30. 30. Soghli, N., Yousefi, T., Abolghasemi, M., et al. (2021). NORAD, a critical long non-coding RNA in human cancers. Life Sciences, 264, 118665. [CrossRef]
31. 31. Wang, S., Wang, Y., Zhang, Z., et al. (2021). Long non-coding RNA NRON promotes tumor proliferation by regulating ALKBH5 and nanog in gastric cancer. Journal of Cancer, 12(22), 6861. [CrossRef]
32. 32. Arunima, A., van Schaik, E.J., Samuel, J.E. (2023). The emerging roles of long non-coding RNA in host immune response and intracellular bacterial infections. Frontiers in Cellular and Infection Microbiology, 13, 1160198. [CrossRef]
33. 33. Zeng, M., Wu, Y., Lu, C., et al. (2022). DeepLncLoc: A deep learning framework for long non-coding RNA subcellular localization prediction based on subsequence embedding. Briefings in Bioinformatics, 23(1), bbab360. [CrossRef]
34. 34. Ghavami, S., Zamani, M., Ahmadi, M., et al. (2022). Epigenetic regulation of autophagy in gastrointestinal cancers. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1868(11), 166512. [CrossRef]
35. 35. Huang, W., Li, H., Yu, Q., et al. (2022). LncRNA-mediated DNA methylation: An emerging mechanism in cancer and beyond. Journal of Experimental & Clinical Cancer Research, 41(1), 100. [CrossRef]
36. 36. Ma, F., Lei, Y.Y., Ding, M.G., et al. (2020). LncRNA NEAT1 interacted with DNMT1 to regulate malignant phenotype of cancer cell and cytotoxic T cell infiltration via epigenetic inhibition of p53, cGAS, and STING in lung cancer. Frontiers in Genetics, 11, 250. [CrossRef]
37. 37. Gao, N., Li, Y., Li, J., et al. (2020). Long non-coding RNAs: The regulatory mechanisms, research strategies, and future directions in cancers. Frontiers in Oncology, 10, 598817. [CrossRef]
38. 38. Yang, Q., Chen, Y., Guo, R., et al. (2022). Interaction of ncRNA and epigenetic modifications in gastric cancer: Focus on histone modification. Frontiers in Oncology, 11, 822745. [CrossRef]
39. 39. Zhang, Y., Sun, Z., Jia, J., et al. (2021). Overview of histone modification. Histone Mutations and Cancer, 1-16. [CrossRef]
40. 40. Tan, R.Z., Jia, J., Li, T., et al. (2024). A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone. Biomedicine & Pharmacotherapy, 176, 116922. [CrossRef]
41. 41. Zhou, Y., Sun, W., Qin, Z., et al. (2021). LncRNA regulation: New frontiers in epigenetic solutions to drug chemoresistance. Biochemical Pharmacology, 189, 114228. [CrossRef]
42. 42. Trotman, J.B., Braceros, K.C., Cherney, R.E., et al. (2021). The control of polycomb repressive complexes by long noncoding RNAs. Wiley Interdisciplinary Reviews: RNA, 12(6), e1657. [CrossRef]
43. 43. Shi, Y., Huang, Q., Kong, X., et al. (2021). Current knowledge of long non-coding RNA HOTAIR in breast cancer progression and its application. Life, 11(6), 483. [CrossRef]
44. 44. Balas, M.M., Hartwick, E.W., Barrington, C., et al. (2021). Establishing RNA-RNA interactions remodels lncRNA structure and promotes PRC2 activity. Science Advances, 7(16), eabc9191. [CrossRef]
45. 45. Zhang, X.Z., Liu, H., Chen, S.R. (2020). Mechanisms of long non-coding RNAs in cancers and their dynamic regulations. Cancers, 12(5), 1245. [CrossRef]
46. 46. Liu, Y., Liu, X., Lin, C., et al. (2021). Noncoding RNAs regulate alternative splicing in Cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 11. [CrossRef]
47. 47. Gonzalez, I., Munita, R., Agirre, E., et al. (2015). A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nature Structural & Molecular Biology, 22(5), 370-376. [CrossRef]
48. 48. Bonano, V.I., Oltean, S., Brazas, R.M., et al. (2006). Imaging the alternative silencing of FGFR2 exon IIIb in vivo. Rna, 12(12), 2073-2079. [CrossRef]
49. 49. Gu, P., Chen, X., Xie, R., et al. (2017). lncRNA HOXD-AS1 regulates proliferation and chemo-resistance of castration-resistant prostate cancer via recruiting WDR5. Molecular Therapy, 25(8), 1959-1973. [CrossRef]
50. 50. Zhang, J., Zhu, H., Li, L., et al. (2024). New mechanism of LncRNA: In addition to act as a ceRNA. Non-Coding RNA Research. [CrossRef]
51. 51. Nojima, T., Proudfoot, N.J. (2022). Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics. Nature Reviews Molecular Cell Biology, 23(6), 389-406. [CrossRef]
52. 52. Zheng, X., Chen, Y., Zhou, Y., et al. (2021). Full-length annotation with multistrategy RNA-seq uncovers transcriptional regulation of lncRNAs in cotton. Plant Physiology, 185(1), 179-195. [CrossRef]
53. 53. Ali, T., Grote, P. (2020). Beyond the RNA-dependent function of LncRNA genes. Elife, 9, e60583. [CrossRef]
54. 54. Gan, Y., Wang, L., Liu, G., et al. (2024). Transposable elements contribute to the regulation of long noncoding RNAs in Drosophila melanogaster. Insects, 15(12), 950. [CrossRef]
55. 55. Zong, X., Wang, S., Han, Y., et al. (2021). Genome-wide profiling of the potential regulatory network of lncRNA and mRNA in Melilotus albus under salt stress. Environmental and Experimental Botany, 189, 104548. [CrossRef]
56. 56. Kornienko, A.E., Guenzl, P.M., Barlow, D.P., et al. (2013). Gene regulation by the act of long non-coding RNA transcription. BMC Biology, 11, 1-14. [CrossRef]
57. 57. Shetty, A., Venkatesh, T., Kabbekodu, S.P., et al. (2022). LncRNA–miRNA–mRNA regulatory axes in endometrial cancer: A comprehensive overview. Archives of Gynecology and Obstetrics, 306(5), 1431-1447. [CrossRef]
58. 58. Fan, J., Xing, Y., Wen, X., et al. (2015). Long non-coding RNA ROR decoys gene-specific histone methylation to promote tumorigenesis. Genome Biology, 16, 1-17. [CrossRef]
59. 59. Zhang, C., Ge, S., Gong, W., et al. (2020). LncRNA ANRIL acts as a modular scaffold of WDR5 and HDAC3 complexes and promotes alteration of the vascular smooth muscle cell phenotype. Cell Death & Disease, 11(6), 435. [CrossRef]
60. 60. Jin, L., Pan, Y.L., Zhang, J., et al. (2021). LncRNA HOTAIR recruits SNAIL to inhibit the transcription of HNF4α and promote the viability, migration, invasion and EMT of colorectal cancer. Translational Oncology, 14(4), 101036. [CrossRef]
61. 61. Chen, Y., Li, Z., Chen, X., et al. (2021). Long non-coding RNAs: From disease code to drug role. Acta Pharmaceutica Sinica B, 11(2), 340-354. [CrossRef]
62. 62. Hashemi, M., Moosavi, M.S., Abed, H.M., et al. (2022). Long non-coding RNA (lncRNA) H19 in human cancer: From proliferation and metastasis to therapy. Pharmacological Research, 184, 106418. [CrossRef]
63. 63. Long, F., Li, X., Pan, J., et al. (2024). The role of lncRNA NEAT1 in human cancer chemoresistance. Cancer Cell International, 24(1), 236. [CrossRef]
64. 64. Xu, W.W., Jin, J., Wu, X.Y., et al. (2022). MALAT1-related signaling pathways in colorectal cancer. Cancer Cell International, 22(1), 126. [CrossRef]
65. 65. Bhat, A.A., Afzal, O., Afzal, M., et al. (2024). MALAT1: A key regulator in lung cancer pathogenesis and therapeutic targeting. Pathology-Research and Practice, 253, 154991. [CrossRef]
66. 66. Li, R., Wang, X., Zhu, C., et al. (2022). lncRNA PVT1: A novel oncogene in multiple cancers. Cellular & Molecular Biology Letters, 27(1), 84. [CrossRef]
67. 67. Shigeyasu, K., Toden, S., Ozawa, T., et al. (2020). The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer. Molecular Cancer, 19, 1-6. [CrossRef]
68. 68. Baljon, K. J., Ramaiah, P., Saleh, E.A.M., et al. (2023). LncRNA PVT1: As a therapeutic target for breast cancer. Pathology-Research and Practice, 154675. [CrossRef]
69. 69. Hakami, M.A., Hazazi, A., Khan, F.R., et al. (2024). PVT1 lncRNA in lung cancer: A key player in tumorigenesis and therapeutic opportunities. Pathology-Research and Practice, 253, 155019. [CrossRef]
70. 70. Bohosova, J., Kubickova, A., Slaby, O. (2021). lncRNA PVT1 in the pathogenesis and clinical management of renal cell carcinoma. Biomolecules, 11(5), 664. [CrossRef]
71. 71. Zhou, C., Yi, C., Yi, Y., et al. (2020). LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. Molecular Cancer, 19, 1-24. [CrossRef]
72. 72. Wu, T., Ji, Z., Lin, H., et al. (2022). Noncoding RNA PVT1 in osteosarcoma: The roles of lncRNA PVT1 and circPVT1. Cell Death Discovery, 8(1), 456. [CrossRef]
73. 73. Li, Y., Song, S., Pizzi, M.P., et al. (2020). LncRNA PVT1 is a poor prognosticator and can be targeted by PVT1 antisense oligos in gastric adenocarcinoma. Cancers, 12(10), 2995. [CrossRef]
74. 74. Martínez-Barriocanal, Á., Arango, D., Dopeso, H. (2020). PVT1 long non-coding RNA in gastrointestinal cancer. Frontiers in Oncology, 10, 38. [CrossRef]
75. 75. Lai, S.W., Chen, M.Y., Bamodu, O.A., et al. (2021). Exosomal lncRNA PVT1/VEGFA axis promotes colon cancer metastasis and stemness by downregulation of tumor suppressor miR‐152‐3p. Oxidative Medicine and Cellular Longevity, 2021(1), 9959807. [CrossRef]
76. 76. Chen, M., Zhang, R., Lu, L., et al. (2020). LncRNA PVT1 accelerates malignant phenotypes of bladder cancer cells by modulating miR-194-5p/BCLAF1 axis as a ceRNA. Aging (Albany NY), 12(21), 22291. [CrossRef]
77. 77. Jiang, X., Ning, Q. (2020). The mechanisms of lncRNA GAS5 in cardiovascular cells and its potential as novel therapeutic target. Journal of Drug Targeting, 28(10), 1012-1017. [CrossRef]
78. 78. Zhao, H., Yang, K., Zhang, Y., et al. (2023). APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation. Protein & Cell, 14(12), 908-913. [CrossRef]
79. 79. Yan, Y., Song, D., Song, X., et al. (2020). The role of lncRNA MALAT1 in cardiovascular disease. IUBMB Life, 72(3), 334-342. [CrossRef]
80. 80. Busscher, D., Boon, R.A., Juni, R.P. (2022). The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases. Clinical Science, 136(15), 1157-1178. [CrossRef]
81. 81. Wang, M., Xie, H., Dai, B. (2021). LncRNA ZFAS1 might be a novel therapeutic target in the treatment of cardiovascular disease. International Journal of Cardiology, 337, 99. [CrossRef]
82. 82. Taghizadeh, E., Gheibihayat, S.M., Taheri, F., et al. (2021). LncRNAs as putative biomarkers and therapeutic targets for Parkinson’s disease. Neurological Sciences, 42, 4007-4015. [CrossRef]
83. 83. Cheng, J., Duan, Y., Zhang, F., et al. (2021). The role of lncRNA TUG1 in the Parkinson disease and its effect on microglial inflammatory response. Neuromolecular Medicine, 23, 327-334. [CrossRef]
84. 84. Dibaj, M., Haghi, M., Safaralizadeh, R., et al. (2024). The role of EZH2 and its regulatory lncRNAs as a serum-based biomarker in Alzheimer’s disease. Molecular Biology Reports, 51(1), 866. [CrossRef]
85. 85. Peng, L., Chen, Y., Ou, Q., et al. (2020). LncRNA MIAT correlates with immune infiltrates and drug reactions in hepatocellular carcinoma. International Immunopharmacology, 89, 107071. [CrossRef]
86. 86. Tripathi, D., Singh, M., Pandey-Rai, S. (2022). Crosstalk of nanoparticles and phytohormones regulate plant growth and metabolism under abiotic and biotic stress. Plant Stress, 6, 100107. [CrossRef]
87. 87. Zhang, J., Liao, J., Ling, Q., et al. (2022). Genome-wide identification and expression profiling analysis of maize AP2/ERF superfamily genes reveal essential roles in abiotic stress tolerance. BMC Genomics, 23(1), 125. [CrossRef]
88. 88. Yang, H., Cui, Y., Feng, Y., et al. (2023). Long non-coding RNAs of plants in response to abiotic stresses and their regulating roles in promoting environmental adaption. Cells, 12(5), 729. [CrossRef]
89. 89. Jha, U.C., Nayyar, H., Jha, R., et al. (2020). Long non-coding RNAs: Emerging players regulating plant abiotic stress response and adaptation. BMC Plant Biology, 20, 1-20. [CrossRef]
90. 90. Pradhan, U.K., Meher, P.K., Naha, S., et al. (2023). ASLncR: A novel computational tool for prediction of abiotic stress-responsive long non-coding RNAs in plants. Functional & Integrative Genomics, 23(2), 113. [CrossRef]
91. 91. Baruah, P.M., Kashyap, P., Krishnatreya, D.B., et al. (2021). Identification and functional analysis of drought responsive lncRNAs in tea plant. Plant Gene, 27, 100311. [CrossRef]
92. 92. Chen, J., Zhong, Y., Qi, X. (2021). LncRNA TCONS_00021861 is functionally associated with drought tolerance in rice (Oryza sativa L.) via competing endogenous RNA regulation. BMC Plant Biology, 21, 1-12. [CrossRef]
93. 93. Weidong, Q.I., Hongping, C., Zuozhen, Y., et al. (2020). Systematic characterization of long non-coding RNAs and their responses to drought stress in Dongxiang wild rice. Rice Science, 27(1), 21-31. [CrossRef]
94. 94. Ding, Z., Tie, W., Fu, L., et al. (2019). Strand-specific RNA-seq based identification and functional prediction of drought-responsive lncRNAs in cassava. BMC Genomics, 20, 1-13. [CrossRef]
95. 95. Li, N., Wang, Z., Wang, B., et al. (2022). Identification and characterization of long non-coding RNA in tomato roots under salt stress. Frontiers in Plant Science, 13, 834027. [CrossRef]
96. 96. Shaw, J., Ghosh, P., Bhattacharya, S., et al. (2024). Combined drought and salinity trigger unique lncRNA regulatory signatures in sweet sorghum (Sorghum bicolor L. Moench) compared to individual stress responses. Plant Growth Regulation, 1-18. [CrossRef]
97. 97. Baruah, P.M., Krishnatreya, D.B., Bordoloi, K.S., et al. (2021). Genome wide identification and characterization of abiotic stress responsive lncRNAs in Capsicum annuum. Plant Physiology and Biochemistry, 162, 221-236. [CrossRef]
98. 98. Zhang, X., Dong, J., Deng, F., et al. (2019). The long non-coding RNA lncRNA973 is involved in cotton response to salt stress. BMC Plant Biology, 19, 1-16. [CrossRef]
99. 99. Luo, C., He, B., Shi, P., et al. (2022). Transcriptome dynamics uncovers long non-coding RNAs response to salinity stress in Chenopodium quinoa. Frontiers in Plant Science, 13, 988845. [CrossRef]
100. 100. Grillone, K., Caridà, G., Luciano, F., et al. (2024). A systematic review of non-coding RNA therapeutics in early clinical trials: A new perspective against cancer. Journal of Translational Medicine, 22(1), 731. [CrossRef]