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Published on: March 30, 2019
IGF2BP3 Worsens Lung Cancer through Modifying Long Non-coding RNA CERS6-AS1/microRNA-1202 Axis
An Yan1, Xiaowei Song2, Bao Liu1
1Department of Thoracic Oncology, Harbin Medical University Cancer Hospital, Harbin 150000, Heilongjiang, China.
Background:
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) can epigenetically regulate lung cancer progression, but its regulatory mechanism in the disease lacks sufficient exploration.
Objective:
The study was conducted to probe the regulatory function of IGF2BP3 in lung cancer via modulating the long non-coding RNA CERS6-AS1/microRNA-1202 (CERS6- AS1/miR-1202) axis.
Methods:
Clinical samples were collected to evaluate IGF2BP3, CERS6-AS1, miR-1202 and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) levels. The interactions among IGF2BP3, CERS6-AS1, miR-1202 and GDPD5 were assessed. IGF2BP3-, CERS6-AS1-, and miR-1202-related constructs were transfected into lung cancer cells to determine cell biological functions. Cell tumor formation ability was further detected in vivo.
Results:
High expression of IGF2BP3, CERS6-AS1 and GDPD5, and low expression of miR-1202 levels were witnessed in lung cancer tissues. Suppression of IGF2BP3 restrained lung cancer progression. IGF2BP3 positively modulated CERS6-AS1 to regulate miR-1202-targeted GDPD5. Inhibition of CERS6-AS1 or promotion of miR-1202 depressed lung cancer aggravation. CERS6-AS1 silencing or miR-1202 overexpression reversed the impacts induced by IGF2BP3 on lung cancer.
Conclusion:
IGF2BP3 facilitates the development of lung cancer cells via binding to the CERS6-AS1 promoter and down-regulating miR-1202, which may be related to GDPD5 upregulation.
Insights
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) promotes lung cancer by regulating the CERS6-AS1/miR-1202 axis and upregulating GDPD5. Inhibiting IGF2BP3 or targeting this axis may offer therapeutic strategies for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is implicated in epigenetic regulation of lung cancer.
- The precise molecular mechanisms of IGF2BP3 in lung cancer progression require further elucidation.
Purpose of the Study:
- To investigate the regulatory role of IGF2BP3 in lung cancer.
- To explore the involvement of the long non-coding RNA CERS6-AS1/microRNA-1202 (CERS6-AS1/miR-1202) axis in IGF2BP3-mediated lung cancer development.
Main Methods:
- Analysis of IGF2BP3, CERS6-AS1, miR-1202, and GDPD5 expression in clinical lung cancer samples.
- Assessment of molecular interactions between IGF2BP3, CERS6-AS1, miR-1202, and GDPD5.
- In vitro and in vivo functional assays using transfected lung cancer cells to evaluate the impact of modulating these molecules on tumor growth and progression.
Main Results:
- Elevated levels of IGF2BP3, CERS6-AS1, and GDPD5, with decreased miR-1202, were observed in lung cancer tissues.
- IGF2BP3 positively regulated CERS6-AS1, which in turn affected miR-1202 targeting of GDPD5.
- Suppression of IGF2BP3 or CERS6-AS1, or overexpression of miR-1202, inhibited lung cancer progression and reversed IGF2BP3-induced effects.
Conclusions:
- IGF2BP3 promotes lung cancer cell development by binding to the CERS6-AS1 promoter, leading to down-regulation of miR-1202.
- This pathway may involve the upregulation of glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5).
- Targeting the IGF2BP3/CERS6-AS1/miR-1202/GDPD5 axis presents a potential therapeutic strategy for lung cancer.
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