Upregulated METTL3 promotes metastasis of colorectal Cancer via miR-1246/SPRED2/MAPK signaling pathway.

Abstract:

BACKGROUND:m6A modification has been proved to play an important role in many biological processes. METTL3 as the main methyltransferase for methylation process has been found to be upregulated in many cancers, including CRC. Here, we investigate m6A modification and the underlying mechanism of METTL3 in the development of CRC. METHODS:The expression of METTL3 was detected in large clinical patient samples. To evaluate the function of METTL3 in vitro and in vivo, colony formation, CCK-8, cell migration and invasion assays were performed. To find out the downstream target of METTL3, GEO dataset was re-mined. We analyzed expression and metastasis-related miRNA by Pearson correlation, and miR-1246 was selected. Here, to identify the downstream target of miR-1246, Targetscan and miRWalk were used. RIP and luciferase reporter assay further confirmed SPRED2 as the direct target of miR-1246. RESULTS:We found that upregulated METTL3 is responsible for abnormal m6A modification in CRC and correlates positively with tumor metastasis. The gain- and loss-of-function indicates that METTL3 promotes cell migration and invasion in vitro and in vivo. Additionally, we confirmed that METTL3 can methylate pri-miR-1246, which further promotes the maturation of pri-miR-1246. By using bioinformatics tools, anti-oncogene SPRED2 was identified as the downstream target of miR-1246, wherein downregulated SPRED2 further reverses the inhibition of the MAPK pathway. CONCLUSIONS:The present study demonstrates that the METTL3/miR-1246/SPRED2 axis plays an important role in tumor metastasis and provides a new m6A modification pattern in CRC development.

journal_name

J Exp Clin Cancer Res

authors

Peng W,Li J,Chen R,Gu Q,Yang P,Qian W,Ji D,Wang Q,Zhang Z,Tang J,Sun Y

doi

10.1186/s13046-019-1408-4

subject

Has Abstract

pub_date

2019-09-06 00:00:00

pages

393

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-019-1408-4

journal_volume

38

pub_type

杂志文章
  • Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing mice.

    abstract:BACKGROUND:Metastasis via the lymphatic system is promoted by lymphangiogenesis. Alterations of the lymphatic channels during the progression of metastasis to regional lymph nodes (LNs) remain unexplored. To examine whether tumor-induced LN lymphangiogenesis controls metastasis to regional LNs, we investigated cervical...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-31-83

    authors: Ozasa R,Ohno J,Iwahashi T,Taniguchi K

    更新日期:2012-10-02 00:00:00

  • Prohibitin overexpression predicts poor prognosis and promotes cell proliferation and invasion through ERK pathway activation in gallbladder cancer.

    abstract:BACKGROUND:Prohibitin (PHB), a pleiotropic protein overexpressed in several tumor types, has been implicated in the regulation of cell proliferation, invasive migration and survival. However, PHB expression and its biological function in gallbladder cancer (GBC) remain largely unknown. METHODS:PHB and p-ERK protein ex...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0346-7

    authors: Cao Y,Liang H,Zhang F,Luan Z,Zhao S,Wang XA,Liu S,Bao R,Shu Y,Ma Q,Zhu J,Liu Y

    更新日期:2016-04-16 00:00:00

  • Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer.

    abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer (NSCLC). The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 (Mcl-1) protein stability and ubiquitination remains undefined. METHODS:MTS ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01566-2

    authors: Yu X,Gao F,Li W,Zhou L,Liu W,Li M

    更新日期:2020-04-10 00:00:00

  • Cost of de novo acute myeloid leukemia induction therapy in adults: analysis of EORTC-GIMEMA AML10 and FLANG regimens.

    abstract::Since the social and financial impact of AML therapy is becoming more and more relevant we analyzed the cost of induction therapy of two different regimens. The first one is part of the widely employed EORTC-GIMEMA AML-10 and consists often days of therapy. The second (FLANG) is a short (three day), Fludarabine, Ara-C...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Clavio M,Quintino S,Masoudi B,Carrara S,Cerri R,Pierri I,Canepa L,Miglino M,Muner P,Damasio E,Gobbi M

    更新日期:2001-06-01 00:00:00

  • A possible role of VEGF in osteolytic bone metastasis of hepatocellular carcinoma.

    abstract::The incidence of bone metastasis was around 13% in 404 patients with hepatocellular carcinoma (HCC) who underwent treatment at the National Kyushu Cancer Center between 1988-97, which is a high value among various cancers. This is, in part, due to the prolonged survival time of HCC patients in recent years. Serum vasc...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Iguchi H,Yokota M,Fukutomi M,Uchimura K,Yonemasu H,Hachitanda Y,Nakao Y,Tanaka Y,Sumii T,Funakoshi A

    更新日期:2002-09-01 00:00:00

  • Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway.

    abstract:BACKGROUND:Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0918-9

    authors: Lian Y,Xiong F,Yang L,Bo H,Gong Z,Wang Y,Wei F,Tang Y,Li X,Liao Q,Wang H,Zhou M,Xiang B,Wu X,Li Y,Li X,Chen X,Li G,Guo C,Zeng Z,Xiong W

    更新日期:2018-10-16 00:00:00

  • Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway.

    abstract:BACKGROUND:The cisplatin-resistance is still a main course for chemotherapy failure of lung cancer patients. Cisplatin-resistant cancer cells own higher malignance and exhibited increased metastatic ability, but the mechanism is not clear. In this study, we investigated the effects of Ataxia Telangiectasia Mutated (ATM...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1161-8

    authors: Shen M,Xu Z,Xu W,Jiang K,Zhang F,Ding Q,Xu Z,Chen Y

    更新日期:2019-04-08 00:00:00

  • Mucin 17 inhibits the progression of human gastric cancer by limiting inflammatory responses through a MYH9-p53-RhoA regulatory feedback loop.

    abstract:BACKGROUND:Mucins are key components of the mucosal barrier in the stomach that protects epithelia from carcinogenic effects of chronic inflammation. Analysis of The Cancer Genome Atlas database indicated that mucin-17 (MUC17) was more highly expressed in gastric cancer (GC) specimens, with favourable prognosis for pat...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1279-8

    authors: Yang B,Wu A,Hu Y,Tao C,Wang JM,Lu Y,Xing R

    更新日期:2019-07-01 00:00:00

  • Impact of tumor stage, operative down-staging, tumor grade and radioresponsitivity of the tumor on survival in supratentorial astrocytomas.

    abstract::This retrospective study analyzed specifically the predicting factors for radioresponse and survival in 74 supratentorial astrocytoma patients. As a result of this study, cytoreduction in terms of ODs to T1 or T0 stage level or pre-RT T1 tumor stage along with radioresponse has a positive impact on long-term survival....

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Erkurt E,Tunali C,Erkişi M,Boyer B,Burgurt R

    更新日期:1998-12-01 00:00:00

  • Detection of EGFR mutations in circulating free DNA by PNA-mediated PCR clamping.

    abstract:BACKGROUND:Epidermal growth factor receptor (EGFR)-activating mutations are major determinants in predicting the tumor response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). Noninvasive test for the detection of EGFR mutations is required, especially in NSCLC patients from whom tissue is not...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,多中心研究

    doi:10.1186/1756-9966-32-50

    authors: Kim HR,Lee SY,Hyun DS,Lee MK,Lee HK,Choi CM,Yang SH,Kim YC,Lee YC,Kim SY,Jang SH,Lee JC,Lee KY

    更新日期:2013-08-09 00:00:00

  • Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma.

    abstract:BACKGROUND:Partial epithelial mesenchymal transition (p-EMT) was found to play a potential role in the initial stage of metastasis in human head and neck squamous cell carcinoma (HNSCC). Some long noncoding RNAs (lncRNAs) have been reported to function as promoters or inhibitors of cancer metastasis. This study aimed t...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1254-4

    authors: Xiong HG,Li H,Xiao Y,Yang QC,Yang LL,Chen L,Bu LL,Zhang WF,Zhang JL,Sun ZJ

    更新日期:2019-06-25 00:00:00

  • Chemotherapy and skin reactions.

    abstract:BACKGROUND:New chemotherapic agents and new protocols in oncology have led to an increasing survival rate in patients affected by tumors. However, this increased use has been accompanied by a growth in the incidence of cutaneous side effects and a worsening of patients' quality of life. Appropriate management of skin t...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-31-50

    authors: Fabbrocini G,Cameli N,Romano MC,Mariano M,Panariello L,Bianca D,Monfrecola G

    更新日期:2012-05-28 00:00:00

  • CCDC88A, a prognostic factor for human pancreatic cancers, promotes the motility and invasiveness of pancreatic cancer cells.

    abstract:BACKGROUND:Coiled-Coil Domain Containing 88A (CCDC88A) was identified as a substrate of the serine/threonine kinase Akt that is capable of binding to the actin cytoskeleton. The aim of this study was to investigate the potential role of CCDC88A in the migration and invasiveness of pancreatic ductal adenocarcinoma (PDAC...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0466-0

    authors: Tanouchi A,Taniuchi K,Furihata M,Naganuma S,Dabanaka K,Kimura M,Watanabe R,Kohsaki T,Shimizu T,Saito M,Hanazaki K,Saibara T

    更新日期:2016-12-05 00:00:00

  • Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway.

    abstract:BACKGROUND:Tumor-associated macrophages (TAMs) and tumor cells are important components of the tumor microenvironment. M2 polarization of TAMs, which is a major actor in breast cancer malignancy and metastasis, can be induced by breast cancer cells. However, the potential mechanisms of the interaction between breast ca...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01676-x

    authors: Tao S,Chen Q,Lin C,Dong H

    更新日期:2020-09-17 00:00:00

  • NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues.

    abstract:BACKGROUND:Clear cell renal cell carcinoma (ccRCC) is the most frequently encountered tumor in the adult kidney. Many factors are known to take part in the development and progression of this tumor. Nuclear factor kappa B (NF-kappaB) is a family of the genes that includes five members acting in events such as inflammat...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-27-53

    authors: Meteoglu I,Erdogdu IH,Meydan N,Erkus M,Barutca S

    更新日期:2008-10-19 00:00:00

  • Stimulation of megakaryocytopoiesis and platelet production during growth of an experimental lymphoma.

    abstract::The effect of malignant tumor growth on host's megakaryocytopoiesis and platelet production was studied in mice bearing transplantable Dalton's lymphoma. Tumor growth was paralleled by thrombocytosis, neutrophilia, and anemia. Platelet 51Cr half-life was normal but incorporation of 75Selenomethionine into circulating ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Ray MR

    更新日期:2000-12-01 00:00:00

  • Down-regulated miR-9 and miR-433 in human gastric carcinoma.

    abstract:BACKGROUND:MircoRNAs(miRNAs) are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. METHODS:To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miR...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-28-82

    authors: Luo H,Zhang H,Zhang Z,Zhang X,Ning B,Guo J,Nie N,Liu B,Wu X

    更新日期:2009-06-16 00:00:00

  • miR-589-5p inhibits MAP3K8 and suppresses CD90+ cancer stem cells in hepatocellular carcinoma.

    abstract:BACKGROUND:Cancer stem cells (CSCs) are important in the tumorigenesis and progression of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play crucial roles regulating CD133+ and EpCAM+ CSCs in HCC, although it is unclear whether miRNAs regulate CD90+ CSCs in HCC. METHODS:The miRNA profiles of CD90+ and CD90- HCC c...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0452-6

    authors: Zhang X,Jiang P,Shuai L,Chen K,Li Z,Zhang Y,Jiang Y,Li X

    更新日期:2016-11-11 00:00:00

  • Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research.

    abstract:BACKGROUND:Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. METHODS:Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and bre...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:10.1186/1756-9966-28-79

    authors: Kienle GS,Glockmann A,Schink M,Kiene H

    更新日期:2009-06-11 00:00:00

  • Intraoperative radiotherapy in the conventional linear accelerator room for early breast cancer treatment: an alternative choice in developing countries.

    abstract::Intraoperative radiotherapy with a single dose of electrons (ELIOT) in the conservative treatment of breast cancer is a possibility under evaluation in clinical trials. The costs of the mobile linear accelerator with a robotic arm, used in intraoperative radiotherapy, are prohibitive for poor countries. The aim of thi...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Frasson AL,Zerwes FP,Braga AP,Barbosa FS,Koch HA

    更新日期:2007-09-01 00:00:00

  • JunB promotes cell invasion, migration and distant metastasis of head and neck squamous cell carcinoma.

    abstract:BACKGROUND:While treatment failure in cases of head and neck squamous cell carcinoma (HNSCC) frequently takes the form of locoregional recurrences and distant metastasis, our understanding of the mechanisms of metastasis in HNSCC is limited. We initially performed the upstream and key nodes analysis together with whole...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0284-4

    authors: Hyakusoku H,Sano D,Takahashi H,Hatano T,Isono Y,Shimada S,Ito Y,Myers JN,Oridate N

    更新日期:2016-01-12 00:00:00

  • NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling.

    abstract:BACKGROUND:Kidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers. Previous study had conflict evidences regarding NR1B2 role in cancer, and its expression and biological role in KIRC remained unclear. Our aims were to characterize the role of NR1B2 in KIRC. METHODS:NR1B2 expression in TCGA dat...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1344-3

    authors: Yin L,Li W,Wang G,Shi H,Wang K,Yang H,Peng B

    更新日期:2019-08-07 00:00:00

  • Whole brain radiotherapy with radiosensitizer for brain metastases.

    abstract:PURPOSE:To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. METHODS:A meta-analysis of randomized controlled trials (RCT)...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,meta分析

    doi:10.1186/1756-9966-28-1

    authors: Viani GA,Manta GB,Fonseca EC,De Fendi LI,Afonso SL,Stefano EJ

    更新日期:2009-01-06 00:00:00

  • Adenosquamous carcinoma of the colorectum: report of two cases.

    abstract::Adenosquamous carcinomas of the colorectum are rare neoplasms. Our experience with two cases is presented in this paper. One patient, who complained of bloody stool, was found to have adenocarcinoma in the sigmoid colon. He received a laparoscopy-assisted sigmoidectomy. The histological examination revealed that the t...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Fukui R,Hata F,Yasoshima T,Furuhata T,Honma T,Nakajima F,Nishimori H,Isomura H,Katsuramaki T,Tanaka H,Kobayashi K,Hirata K

    更新日期:2001-06-01 00:00:00

  • Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of β-catenin stabilization in cancer stem cells.

    abstract:BACKGROUND:Pharmacology-based target identification has become a novel strategy leading to the discovery of novel pathological biomarkers. Ellagic acid (EA), a dietary polyphenol compound, exhibits potent anticancer activities; however, the underlying mechanisms remain unclear. The current study sought to determine the...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-017-0635-9

    authors: Wang N,Wang Q,Tang H,Zhang F,Zheng Y,Wang S,Zhang J,Wang Z,Xie X

    更新日期:2017-12-02 00:00:00

  • Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells.

    abstract:BACKGROUND:Cancer-associated fibroblasts (CAFs), the primary component of tumor stroma in tumor microenvironments, are well-known contributors to the malignant progression of gallbladder cancer (GBC). Thrombospondins (THBSs or TSPs) comprise a family of five adhesive glycoproteins that are overexpressed in many types o...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01812-7

    authors: Shi Y,Sun L,Zhang R,Hu Y,Wu Y,Dong X,Dong D,Chen C,Geng Z,Li E,Fan Y

    更新日期:2021-01-06 00:00:00

  • Cisplatin, epirubicin and cyclophosphamide (PEC) in the treatment of advanced ovarian cancer.

    abstract::We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Massacesi C,Bascioni R,Cellerino R,Scartozzi M,Bracci R,Alessandroni P,Antognoli S,Ciavattini A,De Nictolis M,Piga A

    更新日期:2000-03-01 00:00:00

  • Gemcitabine sensitivity-related mRNA expression in endoscopic ultrasound-guided fine-needle aspiration biopsy of unresectable pancreatic cancer.

    abstract:BACKGROUND:The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). METHODS:mRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by E...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-28-83

    authors: Ashida R,Nakata B,Shigekawa M,Mizuno N,Sawaki A,Hirakawa K,Arakawa T,Yamao K

    更新日期:2009-06-16 00:00:00

  • Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types.

    abstract:BACKGROUND:Survivin is known playing a role in drug resistance. However, its role in bortezomib-mediated inhibition of growth and induction of apoptosis is unclear. There are conflicting reports for the effect of bortezomib on survivin expression, which lacks of a plausible explanation. METHODS:In this study, we teste...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-29-8

    authors: Ling X,Calinski D,Chanan-Khan AA,Zhou M,Li F

    更新日期:2010-01-22 00:00:00

  • Clusterin is a potential molecular predictor for ovarian cancer patient's survival: targeting clusterin improves response to paclitaxel.

    abstract:BACKGROUND:Clusterin is a cytoprotective chaperone protein involved in numerous physiological processes, carcinogenesis, tumor growth and tissue remodelling. The purpose of this study was to investigate whether clusterin (CLU), an antiapoptotic molecule, could be a potential predictor molecule for ovarian cancer and wh...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-30-113

    authors: Hassan MK,Watari H,Han Y,Mitamura T,Hosaka M,Wang L,Tanaka S,Sakuragi N

    更新日期:2011-12-20 00:00:00