Long non-coding RNA CASC2 targeting miR-18a suppresses glioblastoma cell growth, metastasis and EMT in vitro and in vivo
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Ó Indian Academy of Sciences (0123456789().,-volV) (0123456789().,-volV)
Long non-coding RNA CASC2 targeting miR-18a suppresses glioblastoma cell growth, metastasis and EMT in vitro and in vivo JUN WANG1, CHAO QIN1, CHEN ZHONG1, YONG WEN1, SHA KE2 and BO LIAO2* 1
Department of Neurosurgery, The First People’s Hospital of Changde City, Changde 415000, Hunan, China
2
Department of Neurology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan, China *Corresponding author (Email, [email protected]) MS received 18 July 2019; accepted 4 August 2020
Long non-coding RNAs (lncRNAs) cancer susceptibility candidate 2 (CASC2) has been characterized as a tumor suppressor in glioma. Although CASC2 may predict the prognosis of glioma patients, the role and mechanism of CASC2 in human glioblastoma remain to be fully illuminated. Expression of CASC2 and miR18a was detected using RT-qPCR. Cell growth was evaluated by MTT assay, colony formation assay, and flow cytometry; metastasis and epithelial-mesenchymal transition (EMT) were determined with transwell assay and Western blot, respectively. The target binding between CASC2 and miR-18a was predicted on Starbase software, and confirmed by luciferase reporter assay and RNA immunoprecipitation. Xenograft experiment measured tumor growth. As a result, CASC2 was downregulated and miR-18a was upregulated in glioblastoma tumor tissues and cells (T98 and A172). Overexpression of CASC2 promoted apoptosis rate and E-cadherin expression, but suppressed cell viability, colony-forming ability, migration, invasion, and expression of N-cadherin and Vimentin in T98 and A172 cells, accompanied with tumor growth inhibition in vivo; whereas, silencing of CASC2 exerted the opposite effect on cell growth, metastasis and EMT of T98 and A172 cells in vitro. However, reintroduction of miR-18a could reverse CASC2 upregulation-mediated suppression on above cell behaviors in vitro. More importantly, miR-18a was a downstream target for CASC2, and was negatively regulated by CASC2. Collectively, this study demonstrated that CASC2 served as tumor suppressor in glioblastoma by inhibiting cell growth, metastasis and EMT both in vitro and in vivo partially via CASC2miR-18a axis. Keywords.
CASC2; cell growth; EMT; glioblastoma; metastasis; miR-18a
1. Introduction Human gliomas, arising from astrocytes or astroglial precursors, represent the major type of primary brain tumors (Yu et al. 2016). Due to the highly invasive growth pattern, glioma is one of the most prevalent and aggressive malignant tumors in human central nervous system with high mortality rate worldwide (Quan et al. 2017). Even though neurosurgery, radiotherapy, and chemotherapy have achieved many advances to deal with glioblastoma, the most malignant type of advanced glioma (grade IV), the rate of recurrence and http://www.ias.ac.in/jbiosci
mortality remains high because of metastasis (Cruceru et al. 2013). Moreover, the prognosis of glioma is poor and the 5-year survival rate of glioma patients in lowgrade (grad
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