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Updated: Oct 6, 2025

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Long noncoding RNA ADIRF antisense RNA 1 upregulates insulin receptor substrate 1 to decrease the aggressiveness of
Lingling Xu1, Yinling Tan2, Fengxia Xu2
1Department of Oncology, Weifang Yidu Central Hospital, Weifang, Shandong China.
Abstract:
An increasing number of studies have supported the critical regulatory actions of long noncoding RNAs (lncRNAs) in osteosarcoma (OS). However, the detailed roles of adipogenesis regulatory factor-antisense RNA 1 (ADIRF-AS1) in OS have not been comprehensively described. Hence, we first detected ADIRF-AS1 expression in OS and evaluated its clinical significance. Functional experiments were then performed to determine the modulatory role of ADIRF-AS1 in OS progression. ADIRF-AS1 was found to be overexpressed in OS, and the overall survival of patients with OS who had high ADIRF-AS1 levels was shorter than that of those with low levels. ADIRF-AS1 knockdown led to restricted proliferation, migration, and invasiveness of OS cells and increased apoptosis. Additionally, ADIRF-AS1 downregulation impeded tumor growth in vivo. Mechanistically, ADIRF-AS1 acted as a competitive endogenous RNA for microRNA-761 (miR-761) that siphoned miR-761 away from its target, namely insulin receptor substrate 1 (IRS1), leading to IRS1 overexpression. Rescue experiments showed that low levels of miR-761 or restoration of IRS1 could neutralize the effects of ADIRF-AS1 ablation in OS cells. In summary, ADIRF-AS1 exacerbates the oncogenicity of the OS cells by targeting the miR-761/IRS1 axis. Our findings may aid in the advancement of lncRNA-directed therapeutics for OS.
Insights
Long noncoding RNA ADIRF-AS1 promotes osteosarcoma (OS) growth by sponging miR-761, leading to increased IRS1. Lowering ADIRF-AS1 expression inhibits OS progression and may offer new therapeutic strategies.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in regulating gene expression.
- The specific functions of adipogenesis regulatory factor-antisense RNA 1 (ADIRF-AS1) in osteosarcoma (OS) remain largely uncharacterized.
- Understanding lncRNA involvement in OS is vital for developing novel therapeutic approaches.
Purpose of the Study:
- To investigate the expression and clinical significance of ADIRF-AS1 in osteosarcoma.
- To elucidate the functional role of ADIRF-AS1 in OS cell progression.
- To explore the underlying molecular mechanism of ADIRF-AS1 in OS.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to detect ADIRF-AS1 expression levels.
- Cell proliferation, migration, invasion, and apoptosis assays.
- In vivo tumor growth experiments in nude mice.
- RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm molecular interactions.
Main Results:
- ADIRF-AS1 was significantly overexpressed in osteosarcoma tissues and associated with shorter patient survival.
- Knockdown of ADIRF-AS1 suppressed OS cell proliferation, migration, and invasion, while promoting apoptosis.
- ADIRF-AS1 functions as a competing endogenous RNA (ceRNA) by sponging miR-761, leading to the upregulation of its target gene, insulin receptor substrate 1 (IRS1).
- Silencing miR-761 or restoring IRS1 expression could reverse the inhibitory effects of ADIRF-AS1 knockdown.
Conclusions:
- ADIRF-AS1 promotes osteosarcoma oncogenicity by regulating the miR-761/IRS1 axis.
- ADIRF-AS1 serves as a potential diagnostic biomarker and therapeutic target for osteosarcoma.
- Targeting the ADIRF-AS1/miR-761/IRS1 pathway may represent a promising strategy for osteosarcoma treatment.
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