Knockdown of the long noncoding RNA XIST suppresses glioma progression by upregulating miR-204-5p

Abstract

Background: Gliomas are the most prevalent primary malignant tumors of the central nervous system. Our previous study showed that miR-204-5p is a tumor suppressor gene in glioma. Bioinformatic analyses suggest that long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) is a potential target gene of miR-204-5p. Methods: We analyzed the expression of XIST and miR-204-5p in glioma tissues and the correlation with glioma grade. A series of in vitro experiments were carried out to elucidate the role of XIST in glioma progression. A mouse xenograft model was established to detect whether knockdown of XIST can inhibit glioma growth. A luciferase assay was performed to determine whether XIST can bind to miR-204-5p and the binding specificity. Cells stably expressing shXIST or shNC were transfected with anti-miR-204-5p or anti-miR-204-5p-NC to evaluate whether XIST mediates the tumor-suppressive effects of miR-204-5p. Results: XIST was upregulated in glioma tissues compared with normal brain tissues (NBTs), while miR-204-5p expression was significantly decreased in glioma tissues compared with NBTs. Both XIST and miR-204-5p expression levels were clearly related to glioma grade, and the expression of XIST was obviously negatively correlated with miR-204-5p expression. Knockdown of XIST inhibited glioma cell proliferation, migration, and invasion, promoted apoptosis of glioma cells, inhibited tumor growth and increased the survival time in nude mice. miR-204-5p could directly bind to XIST and negatively regulate XIST expression. XIST mediated glioma progression by targeting miR-204-5p in glioma cells. XIST crosstalk with miR-204-5p regulated Bcl-2 expression to promote apoptosis. Conclusion: Our results provide evidence that XIST, miR-204-5p and Bcl-2 form a regulatory axis that controls glioma progression and can serve as a potential therapeutic target for glioma.

Potential of long non-coding RNAs as a therapeutic target and molecular markers in glioblastoma pathogenesis

“…Their study reported that overexpression of miR-133a prevented glioma cell proliferation, metastasis and EMT by reducing the expression of SOX4 [ 159 ]. Consistently, other miRNAs, such as miR-429 [ 160 ], miR-210 [ 161 ], miR-92b [ 162 ] and miR-204-5p [ 163 ] may also modulates the expression of XIST in gliomas.…”

Competing Endogenous RNA Networks in Glioma

“…In 2020, four groups reported novel XIST-mediated ceRNETs that promote glioma progression, i.e., XIST/miR-133a/SOX4 ( Luo et al, 2020 ), XIST/miR-126/IRS1 ( Cheng et al, 2020 ), XIST/miR-204-5p/Bcl-2 ( Shen et al, 2020 ), and XIST/miR-329-3p/CREB1 ( Wang Y.P. et al, 2020 ).…”

“…Furthermore, Cheng et al (2020) demonstrated that IRS1 promotes glioma progression by activating the PI3K/AKT pathway. Shen et al (2020) reported that XIST/miR-204-5p/Bcl-2 ceRNET regulates the proliferation, migration, invasion, and apoptosis of glioma cells. XIST can regulate a variety of apoptosis-related genes, including Bax, caspase 3, caspase 9, and Bcl-2; however, only Bcl-2 had been shown to be a direct target of miR-204-5p and was only tested in their study ( Shen et al, 2020 ).…”

X-Inactive-Specific Transcript: Review of Its Functions in the Carcinogenesis

“…Moreover, miR-204-5p has been identified as another target of XIST in glioma cells. Interaction between XIST and miR-204-5p regulates expression of Bcl-2 (Shen et al, 2020). Figure 6 shows the interactions between XIST and miRNAs in glioma cells.…”