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m6A‑mediated LINC02038 inhibits colorectal cancer progression via regulation of the FAM172A/PI3K/AKT pathway via
Wenjun Liu1, Zilang Zhang2, Xitu Luo1
1The First Department of General Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, P.R. China.
Abstract:
Long noncoding RNAs (lncRNAs) are a type of regulatory molecule with potential roles in the development of several different malignancies. However, the underlying mechanisms of lncRNAs in colorectal cancer (CRC) are incompletely understood. The present study investigated the molecular mechanism of LINC02038 in CRC. LINC02038 expression was decreased in CRC tissues compared to the para‑cancerous tissues and LINC02038 overexpression markedly reduced the proliferation, vitality, migration and invasive ability and greatly accelerated apoptosis of colorectal cancer cells. Bioinformatics examination indicated that LINC02038 may have targeted microRNA (miR)‑552‑5p. RNA immunoprecipitation and luciferase reporter assays showed that LINC02038 served as a sponge for miR‑552‑5p, hindering target gene FAM172A of miR‑552‑5p degradation. Moreover, methylated RNA immunoprecipitation (MeRIP)‑qualitative PCR assays revealed that YTHDF2 could identify and regulate the METTL3‑mediated LINC02038 N6‑methyladenosine (m6A) modification and increase its degradation, thereby promoting CRC progression via the PI3K/AKT pathway. Based on the CRC clinical specimens, it was shown that LINC02038 was negatively associated with lymphatic metastasis and distant metastasis. These results revealed that m6A/LINC02038/miR‑552‑5p/FAM172A may be a novel anti‑tumor axis and LINC02038 may serve as a biomarker and treatment option for colorectal cancer.
Insights
Long noncoding RNA LINC02038 acts as a tumor suppressor in colorectal cancer (CRC) by regulating miR-552-5p and FAM172A. Its m6A modification influences CRC progression and metastasis, suggesting it as a potential biomarker.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in various cancers, but their specific roles in colorectal cancer (CRC) require further elucidation.
- Understanding the molecular mechanisms of lncRNAs in CRC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the molecular mechanism of LINC02038 in the progression of colorectal cancer (CRC).
- To explore the potential of LINC02038 as a biomarker and therapeutic target for CRC.
Main Methods:
- Quantitative analysis of LINC02038 expression in CRC tissues and adjacent tissues.
- Cell proliferation, migration, invasion, and apoptosis assays following LINC02038 overexpression.
- Bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assays, and methylated RNA immunoprecipitation (MeRIP)-qPCR to elucidate molecular interactions.
- Correlation analysis between LINC02038 expression and clinicopathological features in CRC patients.
Main Results:
- LINC02038 expression was significantly decreased in CRC tissues.
- Overexpression of LINC02038 suppressed CRC cell proliferation, migration, and invasion while promoting apoptosis.
- LINC02038 acted as a molecular sponge for miR-552-5p, inhibiting the degradation of its target gene, FAM172A.
- METTL3-mediated m6A modification of LINC02038, identified by YTHDF2, promoted CRC progression via the PI3K/AKT pathway.
- Reduced LINC02038 expression correlated with increased lymphatic and distant metastasis in CRC patients.
Conclusions:
- The m6A/LINC02038/miR-552-5p/FAM172A axis represents a novel anti-tumor pathway in colorectal cancer.
- LINC02038 functions as a tumor suppressor and holds potential as a diagnostic biomarker and therapeutic target for CRC.
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