lncRNA AWPPH promotes the migration and invasion of glioma cells by activating the TGF‑β pathway

Abstract

The long noncoding RNA (lncRNA) AWPPH, also termed microRNA-4435-2HG, has been associated with the poor prognosis of patients with hepatocellular carcinoma (HCC), and has been demonstrated to promote the progression of HCC and bladder cancer. The present study aimed to investigate the role of lncRNA AWPPH in glioma. The expression levels of AWPPH in tumor tissues obtained from patients with glioma and in plasma samples obtained from patients with glioma and healthy controls were detected by reverse transcription-quantitative polymerase chain reaction. The plasma levels of transforming growth factor (TGF)-β1 were measured by an enzyme-linked immunosorbent assay. An AWPPH expression vector was transfected into human glioma cell lines. Subsequently, cancer cell migration and invasion were assessed by Transwell migration and invasion assays, respectively. The expression of TGF-β1 in the transfected-glioma cells was detected by western blot analysis. It was identified that AWPPH expression levels in tumor tissues were higher in patients with metastatic glioma; however, no significant differences in AWPPH expression were revealed between patients with different tumor sizes. The plasma levels of AWPPH were positively correlated with the plasma levels of TGF-β1 in patients with glioma but not in healthy controls. In addition, AWPPH overexpression enhanced cancer cell migration and invasion, and upregulated TGF-β1 expression. Treatment with TGF-β1 demonstrated no significant effect on AWPPH expression; however, a TGF-β inhibitor attenuated the effects of AWPPH overexpression on cell migration and invasion. Therefore, the present study proposed that AWPPH may promote the migration and invasion of glioma cells by activating the TGF-β pathway.

MIR4435-2HG Is a Potential Pan-Cancer Biomarker for Diagnosis and Prognosis

“…In tumors of the urinary system, MIR4435-2HG is abnormally upregulated in cancer tissues and cancer cell lines of clear cell renal cell carcinoma and bladder cancer ( 3 , 40 , 41 ). In nervous system tumors, MIR4435-2HG is highly expressed in plasma, cancer tissues and cancer cell lines of glioma ( 42 , 43 ), and in cancer tissues and cancer cell lines of glioblastoma ( Figure 3 ) ( 44 ).…”

“…Overexpression of MIR4435-2HG can up-regulate TGF-β1 and promote the metastasis of 7 kinds of tumors, including oral squamous cell carcinoma (OSCC) ( 7 ), gastric cancer ( 12 ), colorectal adenocarcinoma ( 17 ), and non-small cell lung cancer ( 27 , 28 , 30 ), ovarian cancer ( 32 ), prostate cancer and glioma ( 38 , 43 ). In addition, in OSCC and colorectal adenocarcinoma ( 7 , 17 ), the up-regulation of MIR4435-2HG and TGF-β1 expression can promote tumor growth and metastasis.…”

“…In OSCC ( 7 ), non-small cell lung cancer ( 27 , 28 , 30 ), ovarian cancer ( 32 ), prostate cancer ( 38 ), and glioma ( 43 ), the expression levels of MIR4435-2HG and TGF-β1was positively correlated with each other, while no correlation between MIR4435-2HG and TGF-β1 was found in plasma of healthy persons. Overexpression of MIR4435-2HG can up-regulate the expression of TGF-β1, while exogenous TGF-β1 treatment has no effect on the expression of MIR4435-2HG.…”

“…β-catenin has been shown to interact with TGF-β ( 57 ). Therefore, β-catenin may mediate the interaction between MIR4435-2HG and TGF-β1 ( 32 , 38 , 43 ), but this still needs further research and verification.…”

Long non-coding RNA MIR4435-2HG: a key molecule in progression of cancer and non-cancerous disorders

“…In patients with glioma cancer, a positive correlation was detected between the plasma levels of TGF-β and MIR4435-2HG. Therefore, it may be concluded that MIR4435-2HG is involved in the progression of glioma occur through TGF-β signaling pathway [59]. As a transcription coactivator, tafazzin, phospholipid-lysophospholipid transacylase (TAZ) is one of the most important downstream effectors of the Hippo signaling pathway that regulates cell proliferation, migration, and apoptosis [60].…”