PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer

Hong-Kun Wu1, Chang Liu1, Xin-Xing Li2

  • 1Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, P.R. China.

Aging
|July 8, 2020
PubMed

Insights

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulate PHLPP2 in colon cancer. LINC00402, LINC00461, and SFTA1P act as competing endogenous RNAs (ceRNAs) for PHLPP2, influencing tumor progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The tumor suppressor role of PHLPP2 in colon cancer is established.
  • The involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) in regulating PHLPP2 in colon cancer remains to be fully elucidated.

Purpose of the Study:

  • To investigate the regulatory roles of lncRNAs and miRNAs on PHLPP2 in colon cancer.
  • To explore the potential of PHLPP2, lncRNAs, and miRNAs as therapeutic targets for colon cancer.

Main Methods:

  • Gene expression analysis using RT-qPCR and Western blot.
  • In vitro studies in HT-29 colon cancer cells.
  • In vivo studies using a mouse tumor xenograft model.

Main Results:

  • PHLPP2 was found to be downregulated in colon cancer and is a target of miR-141 and miR-424.
  • Upregulation of PHLPP2 and downregulation of miR-141/miR-424 suppressed colon cancer cell proliferation, migration, invasion, EMT, and promoted apoptosis.
  • LINC00402, LINC00461, and SFTA1P were identified as ceRNAs for PHLPP2 by competitively binding to miR-141 and miR-424, enhancing PHLPP2's suppressive effects.

Conclusions:

  • PHLPP2 exhibits suppressive effects in colon cancer pathogenesis.
  • LINC00402, LINC00461, and SFTA1P function as ceRNAs for PHLPP2 via interaction with miR-141 and miR-424, highlighting a novel regulatory network in colon cancer.

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...
9.6K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.1K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.7K
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.4K
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
430