LncRNA MALAT1 Inhibits Buccal Mucosal Fibroblasts Activities in Oral Submucous Fibrosis

doi:10.13701/j.cnki.kqyxyj.2024.07.010

Abstract

Abstract: Objective: To clarify the effect of long non-coding RNA MALAT1 on the activation ability of buccal mucosal fibroblasts (BMFs) induced by arecoline, and to establish theoretical basis for a new therapeutic pathway to oral submucous fibrosis (OSF). Methods: BMFs were cultured in vitro, and were stimulated with different concentrations of arecoline to construct OSF-disease models at the cellular level. CCK-8 method was used to detect cell viability. BMFs activation was detected by Transwell method and collagen gel shrinkage method. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of α-smooth muscle actin antibody (α-SMA) and lncRNA MALAT1 in BMFs. siRNA-MALAT1 was transiently transfected into BMFs to assess changes in the migration and contraction capacity of BMFs stimulated by arecoline. Results: 10 μg/mL of arecoline was the optimal concentration for constructing OSF-disease models in vitro, when intracellular expression of α-SMA and lncRNA MALAT1 was elevated. Transwell experiments and collagen gel contraction experiments suggested that knockdown lncRNA MALAT inhibited arecoline-induced BMFs contraction and migration. Conclusion: lncRNA MALAT1 plays an important role in arecoline-induced BMFs activation, cell contraction, and migration.

Key words: lncRNA MALAT1, oral submucous fibrosis, arecoline, fibroblasts

LI Yijie, SHAO Yiduo, CAI Yunzhou, WU Guangdong, SUN Tianao, WANG Yuehong. LncRNA MALAT1 Inhibits Buccal Mucosal Fibroblasts Activities in Oral Submucous Fibrosis[J]. Journal of Oral Science Research, 2024, 40(7): 622-628.

References

[1] Shao Y, Miao J, Wang Y. Curcumin in the treatment of oral submucous fibrosis: a systematic review and meta-analysis of randomized controlled trials [J]. Int J Oral Maxillofac Surg, 2024, 53(3):239-250.
[2] Rai A, Shrivastava PK, Kumar A, et al. Comparative effectiveness of medicinal interventions for oral submucous fibrosis: A network meta-analysis [J]. J Stomatol Oral Maxillofac Surg, 2023, 124(3):101423.
[3] Dangore-Khasbage S, Bhowate RR, Khubchandani M. Chemical composition of areca nut and its adverse effects on human health [J]. Cureus, 2023, 15(8):e43739.
[4] Chhabra AK, Sune R, Reche A. Oral submucous fibrosis: A review of the current concepts in management [J]. Cureus, 2023, 15(10):e47259.
[5] 郭峰,翦新春,周晌辉,等.口腔黏膜下纤维性变癌变的病理及临床生物学行为回顾性研究[J].中华口腔医学杂志,2011,46(8):494-497.
[6] Nair U, Bartsch H, Nair J. Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms [J]. Mutagenesis, 2004, 19(4):251-262.
[7] Zeng Y, Luo M, Yao Z, et al. Adiponectin inhibits ROS/NLRP3 inflammatory pathway through FOXO3A to ameliorate oral submucosal fibrosis [J]. Odontology,2024.
[8] Mehjabin A, Kabir M, Micolucci L, et al. MicroRNA in fibrotic disorders: A potential target for future therapeutics [J]. Front Biosci (Landmark Ed), 2023, 28(11):317.
[9] Jiang X. The mechanisms and therapeutic potential of long noncoding RNA NEAT1 in fibrosis [J]. Clin Exp Med, 2023, 23(7):3339-3347.
[10] Su K, Wang N, Shao Q, et al. The role of a ceRNA regulatory network based on lncRNA MALAT1 site in cancer progression [J]. Biomed Pharmacother, 2021, 137:111389.
[11] Thapa R, Afzal O, Afzal M, et al. From lncRNA to metastasis: The MALAT1-EMT axis in cancer progression [J]. Pathol Res Pract, 2024, 253:154959.
[12] Li Y, Liu F, Cai Y, et al. LncRNA MALAT1: A potential fibrosis biomarker and therapeutic target [J]. Crystals, 2021, 11(3):249.
[13] Chang YC, Tai KW, Lii CK, et al. Cytopathologic effects of arecoline on human gingival fibroblasts in vitro [J]. Clin Oral Investig, 1999, 3(1):25-29.
[14] Jeng JH, Lan WH, Hahn LJ, et al. Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro [J]. J Oral Pathol Med, 1996, 25(7):371-375.
[15] Zhou ZS, Li M, Gao F, et al. Arecoline suppresses HaCaT cell proliferation through cell cycle regulatory molecules [J]. Oncol Rep, 2013, 29(6):2438-2444.
[16] Cox S, Vickers ER, Ghu S, et al. Salivary arecoline levels during areca nut chewing in human volunteers [J]. J Oral Pathol Med, 2010, 39(6):465-469.
[17] Chang MC, Ho YS, Lee PH, et al. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential [J]. Carcinogenesis, 2001, 22(9):1527-1535.
[18] 李辉莉,方厂云,苏征.槟榔碱对颊黏膜成纤维细胞增殖及迁移的影响[J].国际口腔医学杂志,2020,47(1):32-36.
[19] Hinz B, Phan SH, Thannickal VJ, et al. The myofibroblast: one function, multiple origins [J]. Am J Pathol, 2007, 170(6):1807-1816.
[20] Sandulache VC, Parekh A, Li-Korotky H, et al. Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-beta1-induced collagen synthesis [J]. Wound Repair Regen, 2007, 15(1):122-133.
[21] Chang MC, Lin LD, Wu HL, et al. Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis-a precancer condition [J]. Carcinogenesis, 2013, 34(5):1096-1104.
[22] Tsai CC, Ma RH, Shieh TY. Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis [J]. J Oral Pathol Med, 1999, 28(2):59-63.
[23] Lu MY, Yu CC, Chen PY, et al. miR-200c inhibits the arecoline-associated myofibroblastic transdifferentiation in buccal mucosal fibroblasts [J]. J Formos Med Assoc, 2018, 117(9):791-797.
[24] Liang Z, Chen Y, Zhao Y, et al. miR-200c suppresses endometriosis by targeting MALAT1 in vitro and in vivo [J]. Stem Cell Res Ther, 2017, 8(1):251.
[25] Li L, Gu L, Yao Z, et al. Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway [J]. Pharm Biol, 2020, 58(1):1244-1251.
[26] Zhang J, Han C, Song K, et al. The long-noncoding RNA MALAT1 regulates TGF-β/Smad signaling through formation of a lncRNA-protein complex with Smads, SETD2 and PPM1A in hepatic cells [J]. PLoS One, 2020, 15(1):e228160.
[27] Yang S, Yao H, Li M, et al. Long non-coding RNA MALAT1 mediates transforming growth factor beta1-induced epithelial-mesenchymal transition of retinal pigment epithelial cells [J]. PLoS One, 2016, 11(3):e152687.
[28] Liu J, Xu L, Zhan X. LncRNA MALAT1 regulates diabetic cardiac fibroblasts through the Hippo-YAP signaling pathway [J]. Biochem Cell Biol, 2020, 98(5):537-547.
[29] 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 [J]. PLoS Genet, 2013, 9(3):e1003368.
[30] Dai X, Chen C, Xue J, et al. Exosomal MALAT1 derived from hepatic cells is involved in the activation of hepatic stellate cells via miRNA-26b in fibrosis induced by arsenite [J]. Toxicol Lett, 2019, 316:73-84.
[31] Yu F, Lu Z, Cai J, et al. MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis [J]. Cell Cycle, 2015, 14(24):3885-3896.
[32] Wang Y, Mou Q, Zhu Z, et al. MALAT1 promotes liver fibrosis by sponging miR-181a and activating TLR4-NF-κB signaling [J]. Int J Mol Med, 2021, 48(6):215.
[33] Hussein MA, Valinezhad K, Adel E, et al. MALAT-1 is a key regulator of epithelial-mesenchymal transition in cancer: A potential therapeutic target for metastasis [J]. Cancers (Basel), 2024, 16(1):234.
[34] Shu B, Zhou YX, Li H, et al. The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis [J]. Cell Death Discov, 2021, 7(1):368.
[35] Zhang Y, Wang F, Chen G, et al. LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis [J]. Cell Biosci, 2019, 9:54.
[36] Liu B, Qiang L, Wang GD, et al. LncRNA MALAT1 facilities high glucose induced endothelial to mesenchymal transition and fibrosis via targeting miR-145/ZEB2 axis [J]. Eur Rev Med Pharmacol Sci, 2019, 23(8):3478-3486.