Emerging Role of Human Long Non-coding RNA HOST2 as a Regulator and Biomarker across Multiple Cancer Types

Abstract:

Long non-coding RNAs (lncRNAs) have emerged as important regulators of tumor initiation and progression. Human ovarian cancer-specific transcript 2 (HOST2), also known as competing endogenous lncRNA 2 for microRNA let-7b (CERNA2), is an oncogenic lncRNA that is aberrantly upregulated in several malignancies. This review summarizes current evidence regarding the expression patterns, clinical relevance, and molecular mechanisms of HOST2 in eight cancer types that have been comparatively well studied, including Stomach Adenocarcinoma (STAD), Pancreatic Adenocarcinoma (PAAD), ovarian serous cystadenocarcinoma (OV), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), non-small cell lung cancer (NSCLC), sarcoma (SARC), glioma, and Breast Invasive Carcinoma (BRCA). Mechanistically, HOST2 promotes malignant phenotypes through multiple pathways, most notably by acting as a competing endogenous RNA (ceRNA) for members of the let-7 miRNA family, thereby regulating downstream oncogenic targets. HOST2 has also been implicated in Epithelial-Mesenchymal Transition (EMT), cell-cycle progression, JAK2/STAT3 signaling, and resistance to anticancer drugs such as gemcitabine and gefitinib. Clinically, elevated HOST2 expression has been associated with advanced tumor stage, lymph node or distant metastasis, and unfavorable overall survival in several cancer types, suggesting potential value as a prognostic biomarker and therapeutic target. However, current evidence is derived predominantly from in vitro and in vivo preclinical studies and relatively small retrospective patient cohorts. Further prospective, multicenter, and mechanistic studies are therefore required to validate the clinical utility of HOST2 and to clarify its cancer-specific regulatory functions.