Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;12(2):9113-9127.
doi: 10.1080/21655979.2021.1977104.

Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway

Xingming Zhong  1 , Yong Cai  1
Affiliations

Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway

Xingming Zhong et al. Bioengineered. 2021 Dec.

Abstract

Glioblastoma (GBM) is the most lethal type of brain cancer. An increasing number of studies suggest that long non-coding RNAs (lncRNAs) are implicated in tumor progression. LncRNA HOXD-AS2 was reported to be highly expressed in glioma and associated with glioma grade and poor prognosis. However, the molecular mechanism remains to be elucidated. In this study, we first analyzed differentially expressed lncRNAs in glioblastoma using RNA-seq dataset (156 GBM samples and 5 adjacent normal samples in TCGA (Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database). HOXD-AS2 was found to be significantly up-regulated in GBM tissues, which was further confirmed in GBM patient tumor samples and GBM cell lines. Silencing HOXD-AS2 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. We further identified and validated miR-3681-5p as a target of HOXD-AS2, and miR-3681-5p was negatively regulated by HOXD-AS2. By negatively affecting miR-3681-5p, HOXD-AS2 could promote the expression of MALT1 to augment the aggressiveness of GBM cells. miR-3681-5p overexpression or MALT1 knockdown attenuated aggressiveness of GBM cells. Importantly, silencing HOXD-AS2 suppressed tumorigenesis of GBM cells in the xenograft mouse model. Collectively, our study clarified the role of miR-3681-5p/MALT1 axis underlying the oncogenic function of lncRNA HOXD-AS2 in GBM. Future work is required to study the mechanism by which HOXD-AS2 is upregulated in GBM cells, which can provide novel insights into therapeutic intervention for GBM treatment.

Keywords: Glioblastoma; LncRNA HOXD‐AS2; MALT1; miR-3681-5p.

PubMed Disclaimer

Conflict of interest statement

No potential conflicts of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
LncRNA HOXD-AS2 expression is significantly up-regulated in GBM tissues and cell lines
Figure 2.
Figure 2.
Knockdown of HOXD-AS2 inhibits GBM cell proliferation, migration and invasion, and promotes cell apoptosis
Figure 3.
Figure 3.
HOXD-AS2 acts as a sponge for miR-3681-5p
Figure 4.
Figure 4.
HOXD-AS2 maintains MALT1 expression via sponging miR-3681-5p
Figure 5.
Figure 5.
miR-3681-5p mimic or MALT1 knockdown attenuates aggressiveness in GBM cells
Figure 6.
Figure 6.
Downregulation of lncRNA HOXD-AS2 inhibits GBM tumor growth
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Costa PM, Cardoso A, Mano M, et al. MicroRNAs in glioblastoma: role in pathogenesis and opportunities for targeted therapies. CNS Neurol Disord Drug Targets. 2015;14(2):222–238. - PubMed
    1. Van Meir EG, Costas G. Hadjipanayis, Andrew D. Norden, Hui-Kuo Shu, Patrick Y. Wen,Jeffrey J. Olson, et al. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60(3):166–193. - PMC - PubMed
    1. Mercer TR, Mattick JS.. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013;20(3):300–307. - PubMed
    1. Thrash-Bingham CA, Tartof KD.. aHIF: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. J Natl Cancer Inst. 1999;91(2):143–151. - PubMed
    1. Kotake Y, T Nakagawa, K Kitagawa, S Suzuki, N Liu, M Kitagawa & Y Xiong. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene. 2011;30(16):1956–1962. - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources