ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation Via Sequestering MiR-301b-3p

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Dec 13

PMID 34900984

Citations 12

Authors

Junqing Chen

Ling Cheng

Weibin Zou

Rong Wang

Xiaojia Wang

Zhanhong Chen

Affiliations

Soon will be listed here.

Abstract

For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells. Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group. Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient's prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1. ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.

Citing Articles

MiR-301b-3p targets and regulates EBF3 to impact the stem-like phenotype of breast cancer cells through glycolysis.

Huang J, Zhen W, Ma X, Ge S, Ma L J Clin Biochem Nutr. 2025; 76(1):25-34.

PMID: 39896160 PMC: 11782780. DOI: 10.3164/jcbn.23-131.

MiR-301b-3p promotes breast cancer development through inhibiting the expression of transforming growth factor-beta receptor 2.

Lou J, Liu X, Xie Y, Wu M, Mao W, Ying X PeerJ. 2024; 12:e18324.

PMID: 39525474 PMC: 11546148. DOI: 10.7717/peerj.18324.

Emerging roles of non-coding RNAs in modulating the PI3K/Akt pathway in cancer.

Hashemi M, Khosroshahi E, Asadi S, Tanha M, Ghatei Mohseni F, Abdolmohammad Sagha R Noncoding RNA Res. 2024; 10:1-15.

PMID: 39296640 PMC: 11406677. DOI: 10.1016/j.ncrna.2024.08.002.

Role of SLC7A11/xCT in Ovarian Cancer.

Fantone S, Piani F, Olivieri F, Rippo M, Sirico A, Di Simone N Int J Mol Sci. 2024; 25(1).

PMID: 38203758 PMC: 10779187. DOI: 10.3390/ijms25010587.

A new ferroptosis-related signature model including messenger RNAs and long non-coding RNAs predicts the prognosis of gastric cancer patients.

Liu Y, Liu Y, Ye S, Feng H, Ma L J Transl Int Med. 2023; 11(2):145-155.

PMID: 38025952 PMC: 10680379. DOI: 10.2478/jtim-2023-0089.

References

Bournazou E, Bromberg J . Targeting the tumor microenvironment: JAK-STAT3 signaling. JAKSTAT. 2013; 2(2):e23828. PMC: 3710325. DOI: 10.4161/jkst.23828. View

Xing Y, Zhao Z, Zhu Y, Zhao L, Zhu A, Piao D . Comprehensive analysis of differential expression profiles of mRNAs and lncRNAs and identification of a 14-lncRNA prognostic signature for patients with colon adenocarcinoma. Oncol Rep. 2018; 39(5):2365-2375. DOI: 10.3892/or.2018.6324. View

Du W, Wang S, Zhou Q, Li X, Chu J, Chang Z . ADAMTS9 is a functional tumor suppressor through inhibiting AKT/mTOR pathway and associated with poor survival in gastric cancer. Oncogene. 2012; 32(28):3319-28. DOI: 10.1038/onc.2012.359. View

Panni R, Sanford D, Belt B, Mitchem J, Worley L, Goetz B . Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother. 2014; 63(5):513-28. PMC: 3994288. DOI: 10.1007/s00262-014-1527-x. View

Sun Y, Zhao Z, Yang Z, Xu F, Lu H, Zhu Z . Risk Factors and Preventions of Breast Cancer. Int J Biol Sci. 2017; 13(11):1387-1397. PMC: 5715522. DOI: 10.7150/ijbs.21635. View

Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S . Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012; 67(4):658-64. DOI: 10.1016/j.jaad.2011.12.018. View

Liu J, Zhang X, Wu X . miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes , , and . Mol Ther Oncolytics. 2018; 11:14-19. PMC: 6169426. DOI: 10.1016/j.omto.2018.08.001. View

Ocak Z, Acar M, Gunduz E, Gunduz M, Demircan K, Uyeturk U . Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells. Eur Rev Med Pharmacol Sci. 2013; 17(9):1185-90. View

Zhou Z, Wu X, Zhou Y, Yan W . Long non-coding RNA ADAMTS9-AS1 inhibits the progression of prostate cancer by modulating the miR-142-5p/CCND1 axis. J Gene Med. 2021; 23(5):e3331. DOI: 10.1002/jgm.3331. View

10.

Fatica A, Bozzoni I . Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2013; 15(1):7-21. DOI: 10.1038/nrg3606. View

11.

Lo P, Leung A, Kwok C, Cheung W, Ko J, Yang L . Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene. 2006; 26(1):148-57. DOI: 10.1038/sj.onc.1209767. View

12.

Zhou B, Guo W, Sun C, Zhang B, Zheng F . Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway. Cell Death Dis. 2018; 9(6):706. PMC: 5999603. DOI: 10.1038/s41419-018-0724-5. View

13.

Laulin J, BRUDIEUX R . Atrial natriuretic factor is unlikely to be involved in the reduced aldosterone production in the Brattleboro rat. Regul Pept. 1990; 31(3):157-65. DOI: 10.1016/0167-0115(90)90002-e. View

14.

Chung S, Giehl N, Wu Y, Vadgama J . STAT3 activation in HER2-overexpressing breast cancer promotes epithelial-mesenchymal transition and cancer stem cell traits. Int J Oncol. 2013; 44(2):403-11. PMC: 3898805. DOI: 10.3892/ijo.2013.2195. View

15.

Shen S, Li K, Liu Y, Yang C, He C, Wang H . Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1. Mol Oncol. 2019; 13(12):2554-2573. PMC: 6887590. DOI: 10.1002/1878-0261.12555. View

16.

Zhou H, Wu G, Ma X, Xiao J, Yu G, Yang C . Attenuation of TGFBR2 expression and tumour progression in prostate cancer involve diverse hypoxia-regulated pathways. J Exp Clin Cancer Res. 2018; 37(1):89. PMC: 5921809. DOI: 10.1186/s13046-018-0764-9. View

17.

Ao X, Jiang M, Zhou J, Liang H, Xia H, Chen G . lincRNA‑p21 inhibits the progression of non‑small cell lung cancer via targeting miR‑17‑5p. Oncol Rep. 2018; 41(2):789-800. PMC: 6312999. DOI: 10.3892/or.2018.6900. View

18.

Mercer T, Dinger M, Mattick J . Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009; 10(3):155-9. DOI: 10.1038/nrg2521. View

19.

Boo L, Ho W, Ali N, Yeap S, Ky H, Chan K . MiRNA Transcriptome Profiling of Spheroid-Enriched Cells with Cancer Stem Cell Properties in Human Breast MCF-7 Cell Line. Int J Biol Sci. 2016; 12(4):427-45. PMC: 4807162. DOI: 10.7150/ijbs.12777. View

20.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View