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.

Molecular Medicine Reports
|December 12, 2018
PubMed

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.

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.9K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.8K
What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
196.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.8K
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.8K
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.6K