MicroRNA-136-3p inhibits glioma tumorigenesis in vitro and in vivo by targeting KLF7

Abstract

Background: Malignant brain tumors have been a serious threat to human health worldwide. This study aims to investigate the role of miR-136-3p in glioma development. Methods: Hematoxylin-eosin staining (H&E) staining was used to determine the pathologic alterations of glioma tissues. Quantitative real-time PCR (qRT-PCR) analysis and GEO2R analysis was performed to examine the expression of miRNAs and genes. Western blot was applied to detect the protein expression. Cell counting kit-8 (CCK-8) and colony formation were used to analyze the glioma cell growth. Trans-well assay was used to determine the cell migration. Annexin V-FITC/PI staining was conducted to determine the cell apoptosis of transfected glioma cells. The dual-luciferase reporter assay was carried out to confirm the binding sites of miR-136-3p on 3′ untranslated regions (3′ UTR) of Kruppel-like factor 7 (KLF7). Tumor-bearing experiment in nude mice was performed to comprehensively investigate the role of miR-136-3p/KLF7 axis in gliomas. Results: Firstly, the results showed that miR-136-3p was decreased in glioma tissues compared with adjacent tissues. Overexpression of miR-136-3p significantly inhibited cell growth of LN-229 and U251 by decreasing expression of Cyclin A1 and PCNA (proliferating cell nuclear antigen), and it suppressed glioma cell migration by downregulating N-cadherin and elevating E-cadherin levels, and it also promotes glioma cell apoptosis by promoting Bcl2-associated X (Bax) expression but suppressing Bcl-2 expression. Furthermore, we observed that KLF7 was a direct target of miR-136-3p, and KLF7 was negatively regulated by miR-136-3p in glioma cells. Finally, overexpression of KLF7 partly blocked miR-136-3p-induced inhibition of tumor growth in vitro and in vivo. Conclusions: Targeting miR-136-3p/KLF7 axis might be a novel manner to counter against gliomas.

Identification of miRNAs biomarkers for prostate cancer in serum and tissue based on bioinformatic analysis and experimental validation

“…Recent research suggested that miR-146a-3p is related to the occurrence and progression of disease including asthma, allergic rhinitis and Paget's disease (Duan et al 2023, Xia et al 2023, Stephens et al 2020). Similarly, miR-136-3p is also reported to inhibit tumorigenesis (Xu 2020). However, it hasn't been reported that miR-146a-3p and miR-136-3p may participate in the progression of PCa.…”

Plasma miR-9-3p and miR-136-3p as Potential Novel Diagnostic Biomarkers for Experimental and Human Mild Traumatic Brain Injury

“…Upregulation of miR-136-3p expression was reported in synaptoneurosomes at the preclinical stage of prion disease [ 60 ]. In contrast, downregulation of miR-136-3p expression is observed in glioma tissue of patients with a more aggressive and/or poor prognostic phenotype [ 61 , 62 ]. miR-136 exerts a protective function on neurons in a model of spinal cord ischemia injury [ 63 ].…”

Overexpression of NNMT in Glioma Aggravates Tumor Cell Progression: An Emerging Therapeutic Target

“…H&E staining was performed according to a previously described method [ 30 ]. Briefly, after dewaxing and hydration, a 5 μm longitudinal section was stained with hematoxylin solution for 7 min, soaked in 1% hydrochloric acid in ethanol for 3 s, followed by soaking in 2% ammonia for 10 s. The sections were stained with eosin solution for 5 min and then dehydrated with graded ethanol and xylene.…”