Knockdown of long non-coding RNA HOTAIR inhibits malignant biological behaviors of human glioma cells via modulation of miR-326

Abstract

Glioma is the most common and aggressive primary adult brain tumor. Long non-coding RNAs (lncRNAs) have important roles in a variety of biological properties of cancers. Here, we elucidated the function and the possible molecular mechanisms of lncRNA HOTAIR in human glioma U87 and U251 cell lines. Quantitative RT-PCR demonstrated that HOTAIR expression was up-regulated in glioma tissues and cell lines. Knockdown of HOTAIR exerted tumor-suppressive function in glioma cells. Further, HOTAIR was confirmed to be the target of miR-326 and miR-326 mediated the tumor-suppressive effects of HOTAIR knockdown on glioma cell lines. Moreover, over-expressed miR-326 reduced the FGF1 expression which played an oncogenic role in glioma by activating PI3K/AKT and MEK 1/2 pathways. In addition, the in vivo studies also supported the above findings. Taken together, knockdown of HOTAIR up-regulated miR-326 expression, and further inducing the decreased expression of FGF1, these results provided a comprehensive analysis of HOTAIR-miR-326-FGF1 axis in human glioma and provided a new potential therapeutic strategy for glioma treatment.

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

“…The pathways analysis results showed that there were four pathways related with cancer. In addition, Ke et al also found that the miR-326 was overexpressed after knockdown lncRNA HOTAIR in glioma cells, which reduced FGF1 expression by activating the PI3K/AKT pathway (55). Therefore, our results suggested that these key lncRNAs may play an important role in the progression and development of GC and the cancer genes related pathways.…”

Long noncoding RNA HOXD‐AS2 regulates cell cycle to promote glioma progression

“…Recent evidence indicates that lncRNAs also play important roles in glioma pathogenesis . One of the notable lncRNAs, HOTAIR, plays an important role in regulating glioma cell cycle and progression by interacting with the PRC2 complex in the nucleus or interacting microRNAs in the cytoplasm . HOTAIR is transcribed in an antisense manner with respect to the canonical HOXC genes.…”

Long non‐coding RNAs as an epigenetic regulator in human cancers

“…(6,7) With regard to RNA interactions between lncRNAs and miRNA in cancers, Hox transcript antisense intergenic RNA (HOTAIR), an lncRNA, has an oncogenic role in tumor formation by upregulating fibroblast growth factor 1 by sponging miR-326, which activates the PI3K/AKT and MEK1/2 pathways. (8) We also recently found that Notch1 activation in glioma cells specifically induced the expression of lncRNA for taurine upregulated gene 1 (TUG1), which coordinately promoted self-renewal by sponging miR-145. (9) Thus, accumulating studies of cancer-associated lncRNAs have reported their roles in the multiple pathological steps of tumorigenesis, including cell proliferation, cellular signaling, angiogenesis, and metastasis, which may provide a strong rationale for the targeting of lncRNAs as a specific and potent therapeutic approach to eliminate cancer cells.…”

“…With regard to RNA interactions between lncRNAs and miRNA in cancers, Hox transcript antisense intergenic RNA (HOTAIR), an lncRNA, has an oncogenic role in tumor formation by upregulating fibroblast growth factor 1 by sponging miR‐326, which activates the PI3K/AKT and MEK1/2 pathways . We also recently found that Notch1 activation in glioma cells specifically induced the expression of lncRNA for taurine upregulated gene 1 (TUG1), which coordinately promoted self‐renewal by sponging miR‐145 …”