Role of microRNA-30c Targeting ADAM19 in Colorectal Cancer

Zhang, Qian; Yu, Lei; Qin, Dandan; Huang, Rui; Jiang, Xiaochen; Zou, Chendan; Tang, Qingchao; Chen, Yinggang; Wang, Guiyu; Wang, Xishan; Gao, Xu

doi:10.1371/journal.pone.0120698

Cited by 56 publications

(43 citation statements)

References 41 publications

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“…The cell proliferation assay was performed using a standard procedure [17]. For the colony formation assay, 1000 cells/well were seeded in a 6-well plate in 2 mL complete media for 10 days.…”

Section: Methodsmentioning

confidence: 99%

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

Hu¹,

Wang²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFβ)/SMAD signaling pathway. Methods: RNA sequencing data from the Gene Expression Omnibus database were analyzed using R software. Based on The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort, the clinical significance of MEGF6 was investigated. HCT8R, HCT116, and LoVo CRC cells were transfected with small interfering RNA against MEGF6, and their proliferation and sensitivity to fluorouracil were evaluated with the MTT cell proliferation and colony formation assays. Proteins associated with cell growth were detected by western blot analysis. The apoptosis of cells was evaluated by Annexin V/propidium iodide staining, and transwell assays were performed to assess the involvement of MEGF6 in cell migration. Markers of EMT and TGFβ/SMAD signaling were evaluated by quantitative PCR and western blotting, and the correlation between MEGF6 and these markers was assessed in the TCGA colon and renal adenocarcinoma cohort. Results: The results showed that MEGF6 was upregulated in HCT8R cells. In addition, MEGF6 was significantly overexpressed in tumor tissue and predicted a poor survival in the TCGA-COAD cohort. Moreover, MEGF6 accelerated CRC cell growth and inhibited apoptosis, and promoted CRC metastasis by inducing the EMT. Finally, we found that TGFβ/SMAD signaling triggered the expression of Slug, which regulates the MEGF6-mediated EMT. Conclusions: MEGF6 may serve as an oncogene to promote cell proliferation and inhibit apoptosis. MEGF6 can also accelerate cell migration via TGFβ/SMAD signaling-mediated EMT.

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Section: Methodsmentioning

confidence: 99%

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

Hu¹,

Wang²,

Wang³

et al. 2018

Cell Physiol Biochem

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“…miR-30a promotes tumorigenesis in these cancers by directly targeting tumor-associated proteins. Zhang et al (24) demonstrated that miR-30c inhibited the growth and lung metastasis of colon cancer by targeting ADAM metallopeptidase domain 19. miR-30a has also been reported to target insulin receptor substrate 2 in colorectal tumorigenesis (18). However, the expression and role of miR-30a in the progression of cervical cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Zhao

Shu

et al. 2017

Oncol Lett

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Abstract. Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.

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“…MiR-30e negatively regulates BIRC6 and AVEN, which suppresses the apoptotic activity and it also inhibits Beclin-1 and suppress autophagic process in glioblastoma cell lines [55]. MiR-30c is the member of miR-30 family which inhibited the progression of colon cancer growth by regulating ADAM-19 gene expression [56]. MiR-30c targets several multifaceted cancer associated genes UB69, MTA1 and HBOX1 in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs are main regulators of NF-kB pathway where miR-30e directly target and abrogates the functions of IkBα, a potential inhibitor of NF-kB in prostate cancer. Moreover, miR-30e and miR-30c are evolutionary conserved in varies vertebral species [59,60,56]. In ovarian cancer cells, miR-30c-2-3p targets Activating Transcription Factor 3 (ATF-3) and induces cell proliferation that leads to cancer progression [61].…”

Section: Discussionmentioning

confidence: 99%

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2017

RJLBPCS

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ABSTRACT:The complex history of consensus sequence in microRNA family appears to be closely linked to the early evolution of primates. Each miRNA is predicted to target several hundred genes and the expression pattern of conserved miRNA among species through evolutionary time is an important phenomenon in cancer.Since miRNAs are major post-transcriptional negative regulators of target gene transcript; their origins and functional evolution in primates still remains unclear and controversial. Sixteen miRNAs from seven different types of cancers were analyzed to identify the conserved miRNAs in human and to assess their expression patterns. Evolutionarily conserved sequences were identified among primates for 16 miRNAs by ClustalV algorithm. The expression patterns of 16 miRNAs were confirmed by RT-qPCR. The consensus sequence match was observed in cancer with GU-rich region among globally expressed miRNAs. However, there was an AU-rich region was observed in all sixteen matured miRNAs. Moreover, GU-rich region was observed in stem-loop structured miRNAs. This result indicated that CU-region does not or less evolutionary conserved in cancer and it was replaced by other regions during evolution. The result reveals that these 16 miRNAs showed similar sequence conservation among primates and differentially expressed in seven different types of human cancer cell lines. The present research work reports the sequence conservation of globally expressed miRNA through evolution among primates located on the top branch of the phylogenetic tree and the conserved miRNAs are the major regulators in cancer.

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Role of microRNA-30c Targeting ADAM19 in Colorectal Cancer

Cited by 56 publications

References 41 publications

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

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