HOXB‐AS1 accelerates the tumorigenesis of glioblastoma via modulation of HOBX2 and HOBX3 at transcriptional and posttranscriptional levels

Abstract

Glioblastoma (GBM) is the most universal and invasive brain tumor among adults. Increasing studies have reported that long noncoding RNAs play vital roles in regulating downstream molecules at the transcriptional or posttranscriptional level in tumor progression. The purpose of the current research was to inquire the modulation mechanism by which homeobox B cluster antisense RNA 1 (HOXB-AS1) functioned in GBM. Our study first discovered the lifted expression of HOXB-AS1 and its nearby genes HOXB2 and HOXB3 in GBM and the positive relationship between HOXB-AS1 and HOXB2 or HOXB3. Loss-of-function assays and in vivo study detected that silencing of HOXB-AS1, HOXB2, or HOXB3 restrained the proliferation and induced the apoptosis in GBM. In addition, mechanism experiments demonstrated that HOXB-AS1 recruited interleukin enhancer-binding factor 3 (ILF3) to regulate HOXB2 and HOXB3 expression at the transcriptional level, and HOXB-AS1 sponged miR-186-5p to modulate HOXB2 and HOXB3 expression at posttranscriptional level. Finally, the regulatory mechanism of HOXB-AS1 in GBM was certified through rescue experiments. Our results indicated that HOXB-AS1 boost the HOXB2 or HOXB3 expression at the transcriptional and posttranscriptional levels. We detected the HOXB-AS1-ILF3-HOXB2/HOXB3 axis and HOXB-AS1-miR-186-5p-HOXB2/HOXB3 axis driving the GBM progression, which might generate more effective diagnostic biomarkers and therapeutic targets for patients with GBM.

A Pan-Cancer Landscape of HOX-Related lncRNAs and Their Association With Prognosis and Tumor Microenvironment

“…For Long non-coding RNAs (lncRNAs), as one of the key regulators of cancer, function not only as important molecular markers for cancer prognosis, but also as markers of molecular characteristics at the pan-cancer level. Increasing studies have shown that several lncRNAs affect cancer tumorigenesis and contribute to cancer pathogenesis (Akbari et al, 2020;Bi et al, 2020).…”

Development and Validation of a Novel Stemness-Index-Related Long Noncoding RNA Signature for Breast Cancer Based on Weighted Gene Co-Expression Network Analysis

“…Moreover, Han et al (2020 ) also found that FAM83H-AS1 is associated with triple-negative BC progression by regulating miR-136-5p and MTDH expression. LncRNA HOXB-AS1 can promote the proliferation, migration, and invasion of glioblastoma cells ( Bi et al, 2021 ), multiple myeloma ( Chen R. et al, 2020 ), and endometrial carcinoma ( Liu et al, 2020 ). However, it is less studied in BC.…”

The regulatory role of antisense lncRNAs in cancer

“…Another antisense lncRNA that exerts its function at the transcriptional level is HOXB-AS1 . In glioblastoma (GBM), increased expression of HOXB-AS1 promotes proliferation and induces apoptosis by recruiting transcription factor ILF3 to the promoter regions of HOBX2 and HOBX3 [ 43 ].…”