Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

Abstract

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

Experimental Identification of Aberrantly Expressed Long Non-Coding RNAs in Breast Cancer

“…The lncRNA HOTAIRM1 has already been proposed as a biomarker for oral squamous cell carcinoma [28], and its role in the proliferation and metastasis of breast cancer has also been proposed [29]; the development of resistance to tamoxifen therapy due to the regulation of HOXA1 protein expression is being studied [30].…”

The role of long noncoding RNAs as regulators of the epithelial–Mesenchymal transition process in oral squamous cell carcinoma cells

“…In contrast, higher miR-31 levels predicted nodal metastasis among stage I–III patients ( Tu et al, 2022 ). A close association between HOTAIRM1 and OSCC tumor development has been reported, with this lncRNA serving as a cell cycle regulator and candidate prognostic/therapeutic target in OSCC ( Yu et al, 2021 ). Higher LINC01793 levels are associated with a poorer OSCC prognosis for patients and poor clinicopathological features, showing that this lncRNA is an oncogenic mediator in cancer ( Yuan et al, 2021 ).…”

LncRNA‐HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR‐664b‐3p/Rheb/mTOR pathway

“…Recently, growing evidence has suggested that HOTAIRM1 is an oncogene in multiple cancers and is important in tumorigenesis and development. It has been reported that HOTAIRM1 is upregulated in oral squamous cell carcinoma (OSCC) and enhances OSCC development 13 . HOTAIRM1 is highly expressed in glioblastoma multiforme (GBM) and is closely related to malignancy grade in GBM patients 14 .…”

“…It has been reported that HOTAIRM1 is upregulated in oral squamous cell carcinoma (OSCC) and enhances OSCC development. 13 HOTAIRM1 is highly expressed in glioblastoma multiforme (GBM) and is closely related to malignancy grade in GBM patients. 14 Ye et al demonstrated that HOTAIRM1 was involved in ovarian cancer (OV) development by upregulating MMP9 expression.…”