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Published on: November 28, 2018
Long non‑coding RNA MLK7‑AS1 promotes proliferation in human colorectal cancer via downregulation of p21 expression
Rui Zhang1, Jibin Li1, Xiaofei Yan1
1Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Abstract:
Current studies have highlighted long non‑coding RNAs (lncRNAs) as critical regulators in various cancers, including colorectal cancer (CRC). By utilizing publicly available data from The Cancer Genome Atlas dataset, MLK7 antisense RNA 1 (MLK7‑AS1) was identified as a novel lncRNA that correlated with CRC progression. The results of reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) revealed a significant upregulation of MLK7‑AS1 in both CRC tissue samples and cell lines. In addition, a positive correlation was observed between increased MLK7‑AS1 expression and several clinicopathological factors in patients with CRC. Importantly, MLK7‑AS1 knockdown suppressed CRC cell proliferation and promoted G1/G0 phase arrest and apoptosis in vitro, whereas MLK7‑AS1 overexpression exhibited opposite effects. Consistently, decreased MLK7‑AS1 expression inhibited tumor growth in vivo. Furthermore, RT‑qPCR and western blot assays revealed that p21 may be a potential downstream target of MLK7‑AS1. To the best of the authors' knowledge, this is the first study to report that MLK7‑AS1 has potential as a biomarker and may promote proliferation in CRC partially through downregulating p21 expression.
Insights
Long non-coding RNA MLK7-AS1 is upregulated in colorectal cancer (CRC) and promotes tumor growth by downregulating p21. This study identifies MLK7-AS1 as a potential biomarker for CRC progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are increasingly recognized as key players in cancer development.
- Colorectal cancer (CRC) pathogenesis involves complex molecular alterations, including dysregulation of lncRNAs.
Purpose of the Study:
- To investigate the role of MLK7 antisense RNA 1 (MLK7-AS1) in colorectal cancer progression.
- To explore MLK7-AS1 as a potential diagnostic biomarker for CRC.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) dataset for lncRNA expression in CRC.
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to assess MLK7-AS1 levels in CRC tissues and cell lines.
- In vitro and in vivo experiments involving MLK7-AS1 knockdown and overexpression in CRC models.
- Western blot analysis to examine downstream targets, including p21.
Main Results:
- MLK7-AS1 was identified as a novel lncRNA significantly upregulated in CRC tissues and cell lines.
- Increased MLK7-AS1 expression correlated positively with advanced clinicopathological features in CRC patients.
- MLK7-AS1 knockdown inhibited CRC cell proliferation, induced cell cycle arrest (G1/G0), and promoted apoptosis in vitro.
- MLK7-AS1 overexpression had opposite effects on CRC cell behavior.
- Reduced MLK7-AS1 expression suppressed tumor growth in vivo.
- p21 was identified as a potential downstream target of MLK7-AS1, with MLK7-AS1 potentially downregulating its expression.
Conclusions:
- MLK7-AS1 plays a crucial role in promoting colorectal cancer proliferation and progression.
- MLK7-AS1 may serve as a potential prognostic biomarker for CRC.
- The oncogenic function of MLK7-AS1 in CRC may be partly mediated through the downregulation of the tumor suppressor p21.
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