Long Non-Coding RNA SNHG6 Supports Glioma Progression Through Upregulation of Notch1, Sox2, and EMT

Abstract

Gliomas, particularly the advanced grade glioblastomas, have poor 5-year survival rates and worse outcomes. lncRNAs and EMT have been extensively studied in gliomas but the disease progression remains poorly understood. SNHG6 has been shown to affect glioma cell proliferation but its effect on EMT of glioma cells along with its effect on disease progression is not known. We screened four glioma cell lines; H4, A172, U87MG, and SW088 and grouped them based on high vs. low SNHG6 expression. Transfections with SNHG6 specific siRNA resulted in induction of apoptosis of high SNHG6 expressing A172 and U87MG cells. This was accompanied by inhibition of EMT and downregulation of EMT-modulating factor Notch1, β-catenin activity and the cancer stem cell marker Sox2. The regulation was not found to be reciprocal as silencing of Notch1 and Sox2 failed to affect SNHG6 levels. The levels of SNHG6 and Notch1 were also found elevated in Grade IV glioma patients (n = 4) relative to Grade II glioma patients (n = 5). These results identify SNHG6 and Notch1 as valid targets for glioma therapy.

SOX2 in Glioblastoma: Regulation Mechanisms and A Potential Therapeutic Target

“…Furthermore, silencing of MIAT downregulated the expression of stem factors, followed by upregulation of their downstream miRNAs, let-7a-5p and miR-29b-3p [71]. This is consistent with SNHG6, a lncRNA that supports GBM progression by upregulating SOX2 [72]. Circular RNAs (CircRNAs) are a class of noncoding RNAs with stable loop contractures (Shen et al, 2019) [73].…”

Long noncoding RNA SNHG6 promotes the malignant phenotypes of ovarian cancer cells via miR-543/YAP1 pathway

“…And downregulation of SNHG6 elevated E-cadherin expression, but suppressed levels of N-cadherin and vimentin. Previous studies also reported that high levels of SNHG6 promoted EMT in other cancers, such as breast cancer [ 12 ], colorectal cancer [ 22 ], glioma [ 23 ] and gastric cancer [ 24 ]. The underlying molecular mechanisms by which SNHG6 promoted EMT were varied.…”

Predicting prognosis and immune status in sarcomas by identifying necroptosis-related lncRNAs

“…SNHG6 regulates the proliferation and migration of non-small cell lung cancer [49]. SNHG6 regulated the progression of glioma through upregulation of Notch1, Sox2, and EMT [50]. Nevertheless, the function of SNHG6 as a necroptotic gene in sarcoma has not yet been elucidated.…”