Cite this article
Journal Browser
Volume | Year
News and Announcements
View All

Regulatory role of lncRNA MALAT1 and miR-150-3p interaction in breast cancer progression and therapeutic implications

Krishnamoorthy Vignesh1* Pattusamy Thangamalar1
Show Less
1 Department of Noi Naadal, Government Siddha Medical College, Tirunelveli, Tamil Nadu, India
CP 2024, 6(1), 2633
Submitted: 4 January 2024 | Accepted: 4 February 2024 | Published: 23 April 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Long non-coding RNAs (lncRNAs) play crucial roles in cancer progression and metastasis. However, the precise regulatory mechanisms of MALAT1, an lncRNA, in breast cancer remain elusive. Consequently, this study explored the specific role of MALAT1 as a tumor promoter in breast cancer. Initially, MALAT1-small interfering RNA (siRNA) transfection resulted in the inhibition of breast cancer cell migration, colony formation, and invasion. Real-time polymerase chain reaction analysis also revealed increased E-cadherin expression and decreased vimentin and vascular endothelial growth factor (VEGF) mRNA levels subsequent to the transfection. Bioinformatic analysis further uncovered a specific interaction between MALAT1 and miR-150-3p, indicating elevated MALAT1 expression in breast cancer with a negative correlation to miR-150-3p expression. Furthermore, the overexpression of MALAT1 markedly suppressed miR-150-3p expression, indicating a reciprocal inhibition between the two. Luciferase reporter assays confirmed the specific association between miR-150-3p and MALAT1 at the sequence level. Furthermore, transfection with miR-150-3p mimic inhibited breast cancer cell migration, colony formation, and invasion, along with increased E-cadherin expression and decreased Vimentin and VEGF mRNA levels. Conversely, miR-150-3p inhibitor transfection led to opposing effects, reducing E-cadherin expression, and elevating vimentin and VEGF mRNA levels, while also inhibiting migration, colony formation, and invasion. Functionally, MALAT1 siRNA restrained breast cancer cell proliferation and migration while enhancing cellular apoptosis on administration to breast cancer cells, primarily mediated through miR-150-3p. Our findings delineate MALAT1 as a tumor growth-promoting gene antagonized by miR-150-3p. Building on these insights, this study proposes a potential therapeutic avenue for breast cancer treatment.

Breast cancer
  1. Barzaman K, Karami J, Zarei Z, et al. Breast cancer: Biology, biomarkers, and treatments. Int Immunopharmacol. 2020;84:106535. doi: 10.1016/j.intimp.2020.106535


  1. Katsura C, Ogunmwonyi I, Kankam HK, Saha S. Breast cancer: Presentation, investigation and management. Br J Hosp Med (Lond). 2022;83(2):1-7. doi: 10.12968/hmed.2021.0459


  1. Sideris N, Dama P, Bayraktar S, Stiff T, Castellano L. LncRNAs in breast cancer: A link to future approaches. Cancer Gene Ther. 2022;29(12):1866-1877. doi: 10.1038/s41417-022-00487-w


  1. Jin H, Du W, Huang W, et al. lncRNA and breast cancer: Progress from identifying mechanisms to challenges and opportunities of clinical treatment. Mol Ther Nucleic Acids. 2021;25:613-637. doi: 10.1016/j.omtn.2021.08.005


  1. Hou L, Tu J, Cheng F, et al. Long noncoding RNA ROR promotes breast cancer by regulating the TGF-β pathway. Cancer Cell Int. 2018;18:142. doi: 10.1186/s12935-018-0638-4


  1. Xue ST, Zheng B, Cao SQ, et al. Long non-coding RNA LINC00680 functions as a ceRNA to promote esophageal squamous cell carcinoma progression through the miR- 423-5p/PAK6 axis. Mol Cancer. 2022;21(1):69. doi: 10.1186/s12943-022-01539-3


  1. Ashrafizaveh S, Ashrafizadeh M, Zarrabi A, et al. Long non-coding RNAs in the doxorubicin resistance of cancer cells. Cancer Lett. 2021;508:104-114. doi: 10.1016/j.canlet.2021.03.018


  1. Wu X, Zhang Y, Liang G, Ye H. Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer. Front Pharmacol. 2023;14:1199883. doi: 10.3389/fphar.2023.1199883


  1. Wang X, He H, Rui W, Xie X, Wang D, Zhu Y. Long non-coding RNA MALAT1 binds to miR-150-3p and targets TLX1 to promote the progression of bladder cancer. Onco Targets Ther. 2020;13:2483-2490. doi: 10.2147/OTT.S232965


  1. Ouyang S, Zhou X, Chen Z, Wang M, Zheng X, Xie M. LncRNA BCAR4, targeting to miR-665/STAT3 signaling, maintains cancer stem cells stemness and promotes tumorigenicity in colorectal cancer. Cancer Cell Int. 2019;19:72. doi: 10.1186/s12935-019-0784-3


  1. Yang H, Yan L, Sun K, et al. lncRNA MALAT1 increases viability, invasion, and migration of non-small cell lung cancer cells by targeting glioma-associated oncogene 2 (MALAT1). Oncol Res. 2019;27(3):359-369. doi: 10.3727/096504018X15220594629967


  1. Godinho MF, Sieuwerts AM, Look MP, et al. Relevance of MALAT1 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010;103(8):1284-1291. doi: 10.1038/sj.bjc.6605884


  1. Wang L, Chunyan Q, Zhou Y, et al. MALAT1 increase cisplatin resistance and predicted poor survival in gastric cancer patients. Eur Rev Med Pharmacol Sci. 2021;25(7):2822. doi: 10.26355/eurrev_202104_25517


  1. Ju L, Zhou YM, Yang GS. Up-regulation of long non-coding RNA MALAT1 predicts a poor prognosis in patients with breast cancer, and promotes cell invasion and metastasis. Eur Rev Med Pharmacol Sci. 2016;20(21):4445-4451.


  1. Gan FJ, Li Y, Xu MX, et al. LncRNA MALAT1 expression predicts the clinical response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Cancer Biomark. 2021;32(3):339-351. doi: 10.3233/CBM-210048


  1. Wang JY, Yang Y, Ma Y, et al. Potential regulatory role of lncRNA-miRNA-mRNA axis in breast cancer. Biomed Pharmacother. 2020;121:109627. doi: 10.1016/j.biopha.2019.109627


  1. Vimalraj S, Subramanian R, Dhanasekaran A. LncRNA MALAT1 promotes tumor angiogenesis by regulating MicroRNA-150-5p/VEGFA signaling in breast cancer: In-vitro and in-vivo analyses. Front Oncol. 2021;11:742789. doi: 10.3389/fonc.2021.742789


  1. Chen F, Mo J, Zhang L. Long noncoding RNA MALAT1 promotes breast cancer progression through activating GLI2-dependent gene transcription. Tumour Biol. 2016;37(10):13403-13412. doi: 10.1007/s13277-016-5256-y


  1. Xing Z, Lin A, Li C, et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell. 2014;159(5):1110-1125. doi: 10.1016/j.cell.2014.10.013


  1. Vimalraj S, Partridge NC, Selvamurugan N. A positive role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol. 2014;229(9):1236-1244. doi: 10.1002/jcp.24557


  1. Venkatesh J, Wasson MCD, Brown JM, Fernando W, Marcato P. LncRNA-miRNA axes in breast cancer: Novel points of interaction for strategic attack. Cancer Lett. 2021;509:81-88. doi: 10.1016/j.canlet.2021.04.002


  1. Liang BJ, Lusvarghi S, Ambudkar SV, Huang HC. Use of photoimmunoconjugates to characterize ABCB1 in cancer cells. Nanophotonics. 2021;10(12):3049-3061. doi: 10.1515/nanoph-2021-0252


  1. Yao RW, Wang Y, Chen LL. Cellular functions of long noncoding RNAs. Nat Cell Biol. 2019;21(5):542-551. doi: 10.1038/s41556-019-0311-8


  1. Xu J, Wu KJ, Jia QJ, Ding XF. Roles of miRNA and lncRNA in triple-negative breast cancer. J Zhejiang Univ Sci B. 2020;21(9):673-689. doi: 10.1631/jzus.B1900709


  1. Tufail M. The MALAT1-breast cancer interplay: Insights and implications. Expert Rev Mol Diagn. 2023;23(8):665-678. doi: 10.1080/14737159.2023.2233902


  1. Qin S, Wang Y, Ma C, Lv Q. Competitive endogenous network of circRNA, lncRNA, and miRNA in breast cancer chemoresistance. Eur J Med Res. 2023;28(1):354. doi: 10.1186/s40001-023-01309-x


  1. Li Z, Dou P, Liu T, He S. Application of long noncoding RNAs in breast cancer: Biomarkers and therapeutic targets. Cell Physiol Biochem. 2017;42(4):1407-1419.doi: 10.1159/000479205


  1. Singh D, Assaraf YG, Gacche RN. Long non-coding RNA mediated drug resistance in breast cancer. Drug Resist Updat. 2022;63:100851. doi: 10.1016/j.drup.2022.100851


  1. Shadbad MA, Safaei S, Brunetti O, et al. A systematic review on the therapeutic potentiality of PD-L1-inhibiting MicroRNAs for triple-negative breast cancer: Toward single-cell sequencing-guided biomimetic delivery. Genes (Basel). 2021;12(8):1206. doi: 10.3390/genes12081206
Conflict of interest
The authors declare that they have no competing interests.
Back to top
Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing