MiR-101-3p inhibits EMT to attenuate proliferation and metastasis in glioblastoma by targeting TRIM44
Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear.
Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting.
MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3′UTR.
Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3′UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.
KeywordsGlioblastoma MiR-101-3p TRIM44 EMT
We would like to give our sincere gratitude to the reviewers for their constructive comments.
LL: Guarantor of integrity of the entire study, LL, SMY: study concepts, XZF, CZC: study design, LL, ZSC: definition of intellectual content, SMY, ZSC: literature research, SMY, XZF: clinical studies, SMY, XZF: experimental studies, CZC: data acquisition, CZC, ZSC: data analysis, XZF, CZC: statistical analysis, XZF, CZC: manuscript preparation, LL, SMY: manuscript editing, LL: manuscript review.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 6.Liao H et al (2015) MiR-203 downregulation is responsible for chemoresistance in human glioblastoma by promoting epithelial-mesenchymal transition via SNAI2. Oncotarget 6(11):8914–8928Google Scholar
- 7.Ying Xing QM, Chen X, Zhao Y, Liu W, Jing, Hu, Feng, Xue XW, Cai L (2016) TRIM44 promotes proliferation and metastasis in non-small cell. Oncotarget 7(21):30479–30491Google Scholar
- 9.Chen W et al (2018) Downregulation of miR205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway. Int J Oncol 52(2):485–495Google Scholar
- 12.Smits M et al (2010) miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget 1(8):710–720Google Scholar
- 16.Liu N et al (2017) MicroRNA-101 inhibits proliferation, migration and invasion of human glioblastoma by targeting SOX9. Oncotarget 8(12):19244–19254Google Scholar
- 24.Peng R et al. (2018) Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling. Cancer Med 7:796–808Google Scholar
- 28.Ye Z et al (2016) Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2. Oncotarget 7(25):37524–37535Google Scholar
- 30.Zheng M et al (2015) Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma. Oncotarget 6(9):6797–6810Google Scholar
- 34.Chen W et al (2017) MALAT1-miR-101-SOX9 feedback loop modulates the chemo-resistance of lung cancer cell to DDP via Wnt signaling pathway. Oncotarget 8(55):94317–94329Google Scholar