METTL3 Is Suppressed by Circular RNA circMETTL3/miR-34c-3p Signaling and Limits the Tumor Growth and Metastasis in Triple Negative Breast Cancer

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC.

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Mitotic kinesin-like protein 1, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway

10.21203/rs.3.rs-1228723/v1 ◽

2022 ◽

Author(s):

Zhi Li ◽

Hai-Yan Yang ◽

Xiao-Lan Zhang ◽

Xu Zhang ◽

Yu-Zhou Huang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Cancer Proliferation ◽

Tumor Growth And Metastasis

Abstract Background: Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. MKLP1 plays a crucial role in tumorigenesis and cancer progression. However, the role of MKLP1 in triple negative breast cancer and the underlying mechanism remain unknown. The study aimed to elucidate the biological function regulatory mechanism of MKLP1 in triple negative breast cancerMethods: Quantitative real-time PCR and Western blotting were used to determine the MKLP1 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of MKLP1 on tumor growth and metastasis in triple negative breast cancer. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of MKLP1 in triple negative breast cancer.Results: We found that MKLP1 was significantly up-regulated and associated with poor prognosis in triple negative breast cancer. MKLP1 could promote triple negative breast cancer proliferation, migration and invasion in vitro and in vivo. MKLP1 could activate Wnt/β-catenin pathway and promote EMT progression. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of MKLP1 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. Conclusions: Our findings elucidate WDR5/FOXM1/MKLP1/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

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Circular RNA circ_0014717 Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating miR-668-3p/BTG2 Axis

Frontiers in Oncology ◽

10.3389/fonc.2020.592884 ◽

2021 ◽

Vol 10 ◽

Author(s):

Hongxi Ma ◽

Chunchun Huang ◽

Qiuhuan Huang ◽

Guangzhi Li ◽

Jun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Binding Sites ◽

Close Association ◽

Circular Rna ◽

Migration And Invasion ◽

Biological Processes ◽

Tissue Samples ◽

Qrt Pcr ◽

Direct Binding ◽

Hep3b Cells

Recent studies have reported a close association between circRNAs and cancer development. CircRNAs have been recognized to be involved in various biological processes. Up to now, the function of circRNAs in hepatocellular carcinoma (HCC) is still poorly known. qRT-PCR was used to test circ_0014717 expression in HCC tissue samples and cells was determined. It was shown that circ_0014717 was significantly decreased in HCC. Then, we observed overexpression of circ_0014717 obviously repressed HCC cell growth, migration and invasion. Next, we predicted circ_0014717 acted as a sponge of miR-668-3p. miR-668-3p has been reported to participate in several diseases. In our work, it was shown miR-668-3p was greatly increased in HCC and the direct binding sites between circ_0014717 and miR-668-3p were validated. In addition, B-cell translocation gene 2 (BTG2) is closely involved in cellular carcinogenic processes. BTG2 was predicted as a target for miR-668-3p. By performing rescue assays, we demonstrated that circ_0014717 repressed HCC progression via inhibiting BTG2 expression and sponging miR-668-3p. It was manifested loss of circ_0014717 induced HCC progression, which was reversed by BTG2 in Hep3B cells. In conclusion, our findings illustrated a novel circ_0014717/miR-668-3p/BTG2 regulatory signaling pathway in HCC.

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Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

Cell Death and Disease ◽

10.1038/s41419-021-04193-7 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Chunyu Zhang ◽

Pan Liu ◽

Jiaming Huang ◽

Yuandong Liao ◽

Chaoyun Pan ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Poor Prognosis ◽

Prognostic Biomarker ◽

Circular Rna ◽

Circular Rnas ◽

Inhibit Tumor Growth ◽

Cancer Tumor ◽

Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

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Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma

BioMed Research International ◽

10.1155/2020/7102757 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Zhe-Xiang Wang ◽

Shao-Chun Ren ◽

Zi-Song Chang ◽

Jing Ren

Keyword(s):

Tumor Growth ◽

Cancer Progression ◽

Therapeutic Target ◽

Clinical Stage ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Expression Levels ◽

Human Osteosarcoma ◽

Promising Therapeutic Target ◽

Tumor Growth And Metastasis

Background. Osteosarcoma is known as a type of common human bone malignancy, and more therapeutic targets are still required to combat this disease. In recent years, the involvement of KIF2A in cancer progression has been widely revealed; however, its potential effect on osteosarcoma development remains unknown. This study is to assess the KIF2A expression levels in human osteosarcoma tissues and explore its potential role in osteosarcoma development. Methods. Immunohistochemical (IHC) assays were conducted to evaluate the expression levels of KIF2A in a total of 74 samples of osteosarcoma tissues and adjacent nontumor tissues. According to the staining intensity in tumor tissues, patients were divided into highly expressed and low expression KIF2A groups. The possible links between the KIF2A expression and the clinical pathological features were explored and analyzed, and the effects of KIF2A on osteosarcoma cell proliferation, migration, and invasion were detected through colony formation assay, MTT assay, wound closure assay, and transwell assay, respectively. The effects of KIF2A on tumor growth and metastasis were detected by the use of animal models. Results. KIF2A was highly expressed in human osteosarcoma tissues. Meanwhile, KIF2A was obviously correlated to the tumor size ( P = 0.001 ∗ ) and clinical stage ( P = 0.014 ∗ ) of osteosarcoma patients. Our results also revealed that the ablation of KIF2A dramatically blocked the proliferation, migration, and invasion capacity of osteosarcoma cells in vitro and blocked tumor growth and metastasis in mice. Conclusions. We investigated the involvement of KIF2A in the development and metastasis of osteosarcoma and therefore thought KIF2A as a promising therapeutic target for osteosarcoma treatment.

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Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

Disease Markers ◽

10.1155/2019/6383685 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Fu-Tao Chen ◽

Fu-Kuan Zhong

Keyword(s):

Tumor Growth ◽

Lung Adenocarcinoma ◽

Clinical Stage ◽

Migration And Invasion ◽

Expression Levels ◽

Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

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EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis

Molecular Cancer ◽

10.1186/s12943-018-0911-0 ◽

2018 ◽

Vol 17 (1) ◽

Cited By ~ 77

Author(s):

Renjie Wang ◽

Sai Zhang ◽

Xuyi Chen ◽

Nan Li ◽

Jianwei Li ◽

...

Keyword(s):

Cell Proliferation ◽

Glioblastoma Multiforme ◽

Aurora Kinase ◽

Underlying Mechanism ◽

Circular Rna ◽

Initiation Factor ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Reporter Assays

Abstract Background Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). Methods A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. Results In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. Conclusions Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM. Graphical abstract

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Abstract P1-03-11: Combination ofnab-Paclitaxel and Bevacizumab Inhibited Tumor Growth and Metastasis of a New Triple Negative Breast Cancer Model

10.1158/0008-5472.sabcs10-p1-03-11 ◽

2010 ◽

Author(s):

S Ran ◽

V Trieu ◽

LD Volk ◽

A Wilber ◽

N. Desai

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cancer Model ◽

Breast Cancer Model ◽

Tumor Growth And Metastasis

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LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis

Cancer Cell International ◽

10.1186/s12935-019-1016-6 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 8

Author(s):

Ying Zheng ◽

Bowen Zheng ◽

Xue Meng ◽

Yuwen Yan ◽

Jia He ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Ectopic Expression ◽

Underlying Mechanism ◽

Tongue Squamous Cell Carcinoma ◽

Migration And Invasion

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

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