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Updated: Jan 9, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
ING5-mediated regulation of lung cancer progression via the OIP5-AS1/miR-381-3p/SEC24A axis
Wenxi Cui1, Qihao Wang2, Xin Gongsun3
1College of Arts & Sciences, Oklahoma State University, Stillwater, OK, USA.
Background:
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths globally. It poses a significant threat to human health with high incidence and mortality rates. Current treatments like surgery, chemotherapy, and radiation have limited efficacy and often encounter drug resistance, highlighting the need for new therapeutic targets and strategies. The aim of this study was to assess how ING5 regulates lncOIP5-AS1, miR-381-3p, and SEC24A, and exerts its tumor-suppressive effects.
Methods:
We developed NSCLC cell lines that overexpressed ING5 and transfected them with a miR-381-3p inhibitor and short hairpin RNA (shRNA) targeting long non-coding RNA (lncRNA) OIP5-AS1. The impact of lncRNA OIP5-AS1 on NSCLC cell proliferation, tumorigenesis, and migration was assessed using quantitative real-time polymerase chain reaction (qPCR), Western blot, cell cloning, Cell Counting Kit-8 (CCK-8) test, transwell invasion and migration assay, and subcutaneous tumorigenesis assay in nude mice. Bioinformatics methods were employed to predict the target genes of miR-381-3p, and the interaction with SEC24A was confirmed by a dual luciferase reporter gene test.
Results:
The overexpression of ING5 markedly suppressed the proliferation, migration, and invasion of NSCLC. The inhibitory effect was counteracted by the overexpression of OIP5-AS1. miR-381-3p was markedly increased in cells overexpressing ING5 and interacted with the 3'UTR of SEC24A, suppressing its expression. SEC24A exhibited elevated expression in NSCLC and correlated with unfavorable prognosis. Animal studies demonstrated that the silencing of OIP5-AS1 suppressed tumor proliferation.
Conclusions:
Our cell-based and subcutaneous xenograft experiments suggest that ING5-mediated down-regulation of OIP5-AS1 may release miR-381-3p and consequently reduce SEC24A expression. However, this axis has not yet been validated in clinical specimens, and studies addressing metastasis or long-term toxicity are still needed.
Insights
ING5 suppresses non-small cell lung cancer (NSCLC) by downregulating OIP5-AS1, which releases miR-381-3p to inhibit SEC24A. This pathway offers potential new therapeutic strategies for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Non-small cell lung cancer (NSCLC) presents a significant global health challenge due to high mortality and treatment resistance.
- Existing therapies for NSCLC often have limited efficacy, necessitating the identification of novel therapeutic targets and strategies.
- The tumor suppressor ING5's role in regulating key molecular players in NSCLC requires further elucidation.
Purpose of the Study:
- To investigate the regulatory mechanism of ING5 in NSCLC.
- To assess the interplay between ING5, lncOIP5-AS1, miR-381-3p, and SEC24A in NSCLC.
- To determine the tumor-suppressive effects mediated by this molecular axis.
Main Methods:
- Overexpression of ING5 in NSCLC cell lines.
- Manipulation of lncOIP5-AS1 and miR-381-3p levels using shRNA and inhibitors.
- Assessment of NSCLC cell proliferation, migration, and invasion via qPCR, Western blot, CCK-8, and transwell assays.
- Bioinformatic prediction and dual luciferase reporter assays to confirm miR-381-3p targeting of SEC24A.
- Subcutaneous tumorigenesis assays in nude mice.
Main Results:
- ING5 overexpression significantly inhibited NSCLC cell proliferation, migration, and invasion.
- Overexpression of OIP5-AS1 counteracted the inhibitory effects of ING5.
- ING5 increased miR-381-3p levels, which targeted SEC24A and suppressed its expression.
- SEC24A expression was elevated in NSCLC and associated with poor prognosis.
- Silencing OIP5-AS1 suppressed tumor proliferation in vivo.
Conclusions:
- ING5 exerts tumor-suppressive effects in NSCLC by downregulating OIP5-AS1, thereby releasing miR-381-3p to reduce SEC24A expression.
- This novel molecular axis presents a potential therapeutic target for NSCLC.
- Further validation in clinical specimens and investigation into metastasis and toxicity are warranted.
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