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KITENIN-targeting microRNA-124 suppresses colorectal cancer cell motility and tumorigenesis.

ABSTRACT: MicroRNAs are increasingly implicated in the modulation of the progression of various cancers. We previously observed that KAI1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer (CRC) tissues and hence the functional KITENIN complex acts to promote progression of CRC. However, it remains unknown that microRNAs target KITENIN and whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal tumorigenesis. Here, through bioinformatic analyses and functional studies, we showed that miR-124, miR-27a, and miR-30b negatively regulate KITENIN expression and suppress the migration and invasion of several CRC cell lines via modulation of KITENIN expression. Through in vitro and in vivo induction of mature microRNAs using a tetracycline-inducible system, miR-124 was found to effectively inhibit the invasion of CT-26 colon adenocarcinoma cells and tumor growth in a syngeneic mouse xenograft model. Constitutive overexpression of precursor miR-124 in CT-26 cells suppressed in vivo tumorigenicity and resulted in decreased expression of KITENIN as well as that of MYH9 and SOX9, which are targets of miR-124. Thus, our findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function as endogenous inhibitors of CRC cell motility and demonstrate that miR-124 among KITENIN-targeting microRNAs plays a suppressor role in colorectal tumorigenesis.

SUBMITTER: Park SY

PROVIDER: S-EPMC4435482 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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KITENIN-targeting microRNA-124 suppresses colorectal cancer cell motility and tumorigenesis.

Park So-Yeon SY Kim Hangun H Yoon Somy S Bae Jeong A JA Choi Seok-Yong SY Jung Young Do YD Kim Kyung Keun KK

Molecular therapy : the journal of the American Society of Gene Therapy 20140609 9

MicroRNAs are increasingly implicated in the modulation of the progression of various cancers. We previously observed that KAI1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer (CRC) tissues and hence the functional KITENIN complex acts to promote progression of CRC. However, it remains unknown that microRNAs target KITENIN and whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal tumorigenesis. Here, through bioinformat ...[more]

PMID: 24909917

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Project description:As a member of the integrin family, integrin α3β1 (ITGA3) has been linked to intercellular communication and serves an important role in the signaling among cells and the extracellular matrix. MicroRNA (miR)‑199a‑5p has been demonstrated to be related to the pathogenesis and progression of multiple malignant diseases. However, the biological functions of miR‑199a‑5p and ITGA3 in colorectal cancer (CRC) have rarely been reported. The aim of the present study was to explore the roles of miR‑199a‑5p and ITGA3 in CRC. Immunohistochemistry staining and western blotting were applied to detect the protein expression of ITGA3 in CRC tissues and cells. Reverse transcription‑quantitative PCR was performed to investigate the expression of miR‑199a‑5p and ITGA3 mRNA. HCT‑116 cells were transfected with miR‑199a‑5p mimics, mimics control, short hairpin RNA targeting ITGA3, or pcDNA‑ITGA3 for the functional experiments. Dual luciferase reporter assay was applied to confirm whether miR‑199a‑5p targeted the 3' untranslated region (3'UTR) of ITGA3. The MTT, Transwell and wound healing assays were used to evaluate the proliferation, invasion and migration of CRC cells. Immunofluorescence assay was used to monitor the epithelial‑mesenchymal transition (EMT) biomarker expression. The results demonstrated downregulation of miR‑199a‑5p and upregulation of ITGA3 in CRC tissues and cell lines. miR‑199a‑5p mimics and knockdown of ITGA3 suppressed the proliferation, invasion and migration of CRC cells. Bioinformatics analysis and luciferase reporter assay indicated that miR‑199a‑5p targeted the 3'UTR of the ITGA3 transcript, and overexpression of ITGA3 reversed the tumor‑suppressive effects of miR‑199a‑5p elevation. In addition, the immunofluorescence assay suggested that miR‑199a‑5p mimics suppressed the EMT of CRC cells, whereas the overexpression of ITGA3 restored this effect. In conclusion, miR‑199a‑5p may act as a tumor suppressor by targeting and negatively regulating ITGA3 in CRC.

Dataset Information

KITENIN-targeting microRNA-124 suppresses colorectal cancer cell motility and tumorigenesis.

Publications

KITENIN-targeting microRNA-124 suppresses colorectal cancer cell motility and tumorigenesis.

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