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Updated: Dec 15, 2025

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
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.
Abstract:
Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells in vitro and in mouse tumor xenograft model in vivo. PHLPP2, a target of miR-141 and miR-424, was downregulated in colon cancer. PHLPP2 upregulation and miR-141 and miR-424 downregulation suppressed the colon cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and promote cell apoptosis, which also resulted in suppression of tumor metastasis and formation. Furthermore, LINC00402, LINC00461, and SFTA1P were identified as the targets of miR-141 and miR-424 and acted as competitive endogenous RNAs (ceRNAs) of PHLPP2. The upregulation of LINC00402, LINC00461, and SFTA1P was verified to enhance the suppressive effects of PHLPP2 in the pathogenesis of colon cancer. Conjointly, our results demonstrated the suppressive effects of PHLPP2 in colon cancer and proved that LINC00402, LINC00461, and SFTA1P acted as ceRNAs of PHLPP2 by competitive binding to miR-141 and miR-424.
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.
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lncRNA - Long Non-coding RNAs
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piRNA - Piwi-interacting RNAs
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