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The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma
Mingsheng Ma1, Wei Wang2, Biying Wang1
1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan,650118, China. lhye1204@aliyun.com.
Abstract:
N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.
Insights
RNA-binding motif protein 15 (RBM15) promotes lung adenocarcinoma (LUAD) progression by influencing N6-methyladenosine (m6A) levels. Its knockdown inhibits tumor growth, reduces proliferation, and accelerates apoptosis in LUAD cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- N6-methyladenosine (m6A) is the most prevalent internal modification in mammalian messenger RNAs (mRNAs).
- RNA-binding motif protein 15 (RBM15) is a key methyltransferase involved in m6A modification.
- Growing evidence suggests a correlation between RBM15 and various cancers, including lung cancer, but its specific role in lung adenocarcinoma (LUAD) requires further elucidation.
Purpose of the Study:
- To investigate the expression levels of RBM15 in human LUAD tissues and matched healthy lung tissues.
- To explore the functional role of RBM15 in LUAD cell lines (A549 and H1734) and its association with cellular characteristics and mRNA m6A levels.
- To determine the impact of RBM15 knockdown on LUAD progression both in vitro and in vivo.
Main Methods:
- Analysis of RBM15 expression in human LUAD tissues and cell lines.
- siRNA-mediated knockdown of RBM15 in A549 and H1734 cells.
- Functional assays to assess proliferation, apoptosis, and tumor growth in vitro and in vivo.
- Measurement of mRNA m6A levels following RBM15 knockdown.
Main Results:
- RBM15 was found to be significantly upregulated in LUAD tissues and cells, correlating with poorer patient survival.
- RBM15 knockdown in LUAD cell lines led to decreased mRNA m6A levels.
- In vivo studies demonstrated that RBM15 knockdown inhibited tumor growth, reduced cell proliferation, and promoted apoptosis.
- RBM15 knockdown was successfully achieved using siRNA in A549 cells, enabling further functional characterization.
Conclusions:
- RBM15 plays a crucial role in promoting LUAD cell progression, potentially through m6A demethylation.
- RBM15 upregulation is associated with adverse outcomes in LUAD patients.
- Targeting RBM15 may represent a potential therapeutic strategy for LUAD.
- Further research is warranted to fully understand the downstream molecular mechanisms and regulation of RBM15 activity in LUAC.
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