miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer

Li, Jian; Kong, Fujiao; Wu, Kemin; Song, Kun; He, Jianfeng; Sun, Weijia

doi:10.3892/mmr.2014.2558

Cited by 49 publications

(35 citation statements)

References 32 publications

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“…2). All four of these miRNAs have been reported as dysregulated in other cancer types, including colorectal cancer and pancreatic cancer [19][20][21][22]. In particular, the validity of miR-193b-3p as a prognostic marker in OPSCC was previously reported and incorporated in our previous model for outcome prediction [8].…”

Section: Validation Of An Existing Mirna Prognostic Signaturementioning

confidence: 88%

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

et al. 2016

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Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high‐throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA‐seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA‐seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR‐193b‐3p and miR‐455‐5p were positively associated with survival, and miR‐92a‐3p and miR‐497‐5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4‐miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.

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Section: Validation Of An Existing Mirna Prognostic Signaturementioning

confidence: 88%

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

et al. 2016

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“…MiR-193b is also highly expressed in head and neck squamous cell carcinoma and it was associated to a low disease-free survival in this pathology [33]. Conversely, miR-193b seems to be downregulated in NSCLC, in pancreatic cancer and in breast cancer, suggesting a possible role of this miRNA in the development of these tumors [34][35][36].…”

Section: Discussionmentioning

confidence: 98%

MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

Pinto

Strippoli

Summa

et al. 2015

Expert Opinion on Therapeutic Targets

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Objective: Currently, the treatment of BRAF V600-mutated metastatic melanoma with BRAF inhibitors gives a response rate of ~ 50% with a progression-free survival of ~ 6 -- 7 months. In order to identify predictive biomarkers capable of stratifying BRAF-mutated patients at high risk of shorter response duration to anti-BRAF therapy, the authors analyzed the expression of 15 microRNAs (miRNAs) targeting crucial genes involved in melanoma biology and drug response.Research design and methods: A total of 15 miRNAs and target gene expression were investigated in 43 patients (30 BRAF-mutated, and 13 BRAF wild-type). Moreover, 20 BRAF-mutated patients treated with vemurafenib were analyzed for miRNA expression in respect to time-to-progression.Results: All miRNAs except miR-192 showed low expression in BRAF-mutated as compared with BRAF wild-type patients. In particular, miR-101, miR-221,miR-21, miR-338-3p and miR-191 resulted in significant downregulation inBRAF-mutated patients. Moreover, high expression of miR-192 and miR-193b* and low expression of miR-132 resulted in significant association with shorter progression.Conclusion: Three miRNAs were significantly associated with clinical outcome in metastatic melanoma patients. An increased understanding of the molecular assessment of BRAF-mutated melanomas could allow development of specific molecular tests able to predict response duration.

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“…STMN1 is a 17-kDa cytoplasmic protein, which is also named as oncoprotein 18 (OP18) [41][42][43]. Previous research showed that STMN1 acted as an important regulator in cell cycle, proliferation, invasion and survival through regulating microtubule dynamics [44][45][46]. STMN1 was upregulated in several human tumors such as lung cancer, gastric cancer, oral squamous-cell carcinoma, colorectal tumor, gallbladder cancer and breast cancer [47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1

Wang¹,

Peng²,

Gong³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Increasing evidences suggest that dysregulated expression of miRNAs contributes to the progression of various tumors. However, the underlying function of miR-423-5p in osteosarcoma remains unexplored. Methods: The expression of miR-423-5p and STMN1 were determined in osteosarcoma samples and cell lines via quantitative real-time PCR. Colony formation and Cell Counting Kit-8 (CCK-8) assays were performed to measure cell proliferation ability and transwell analysis was used to detect cell invasion, and dual luciferase reporter assay was perform to analysis the interaction between the miR-423-5p and STMN1. Results: The expression levels of miR-423-5p and STMN1 in the osteosarcoma tissues and cell lines were measured by qRT-PCR. Cell viability was determined using the clone formation and CCK-8 assays. A dual-luciferase reporter and Western blot were performed to stdudy the target gene of miR-423-5p. Here, we showed that miR-423-5p expression was downregulated in osteosarcoma tissues and cell lines. However, the expression of stathmin1 (STMN1) was downregulated in osteosarcoma tissues and cell lines. Moreover, STMN1 expression level was negatively correlated with the miR-423-5p expression in the osteosarcoma tissues. We identified STMN1 was a direct target gene of miR-423-5p in osteosarcoma cell. Overexpression of miR-423-5p inhibited osteosarcoma cell proliferation, colony formation and invasion. Furthermore, we demonstrated that STMN1 was involved in miR-423-5p-mediated cell behavior such as cell proliferation, colony formation and invasion in the osteosarcoma cell. Conclusion: Our present study indicated that miR-423-5p acted as a tumor suppressor gene in osteosarcoma partly through inhibiting STMN1 expression.

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miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer

Cited by 49 publications

References 32 publications

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

MicroRNA expression in BRAF-mutated and wild-type metastatic melanoma and its correlation with response duration to BRAF inhibitors

miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1

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