microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer

Takahashi, Hidekazu; Takahashi, Masanobu; Ohnuma, Shinobu; Unno, Michiaki; Yoshino, Yuki; Ouchi, Kota; Takahashi, Shin; Yamada, Yasuhide; Shimodaira, Hideki; Ishioka, Chikashi

doi:10.1186/s12885-017-3739-x

Cited by 30 publications

(30 citation statements)

References 49 publications

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“…MiR-193a-3p, a member of the miR-193 family, is located at 17q11.2. Recently, it was reported that miR-193a-3p expression was decreased in tumors such as colorectal cancer,17 lung cancer,10 and liver cancer 18. Likewise, we found that miR-193a-3p expression in 37 cases of PDAC tissues was significant lower than in the 42 cases of non-tumor tissues.…”

Section: Discussionsupporting

confidence: 53%

MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1

Chen¹,

Qiao²,

Chen³

et al. 2019

CMAR

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Background: MicroRNAs (miRNAs) could modulate gene expression at the posttranscriptional level by promoting mRNA degradation or blocking mRNA translation, thus affecting the occurrence and development of cancer. Methods: In this work, qRT-PCR was conducted to detect the expression of miR-193a-3p and CCND1 . The ability of cell proliferation was evaluated via CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Bioinformatic techniques were employed to research the regulatory relationship between miR-193a-3p and target genes. The relationship between miR-193a-3p and CCND1 was verified via dual-luciferase reporter assays. Results: MiR-193a-3p expression in pancreatic ductal adenocarcinoma (PDAC) tissue was significantly lower than in non-cancerous tissue. After overexpressing miR-193a-3p in PDAC cells, their multiplication ability was significantly inhibited, apoptosis was accelerated, and the cell cycle was blocked in the G1 and G2/M phases. CCND1 was confirmed to have a targeted relationship with miR-193a-3p. Moreover, CCND1 expression was significantly lower in PDAC cells with an overexpression of miR-193a-3p. Conclusions: MiR-193a-3p targeted CCND1 to suppress tumor growth in PDAC cells. MiR-193a-3p may function as a tumor inhibitor in PDAC development, which could offer a promising therapeutic and prognostic strategy for PDAC treatment.

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Section: Discussionsupporting

confidence: 53%

MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1

Chen¹,

Qiao²,

Chen³

et al. 2019

CMAR

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“…Two studies from well-regarded groups reported that miR-193a-3p was usually under-expressed in CRC cells and acting as a tumor suppressor 17,20. Our previous report extended their finding by identifying that decreased expression of miR-193a-3p was associated with poor prognosis in CRC 21…”

Section: Discussionmentioning

confidence: 55%

“…Dysregulation of miR-193a-3p, a gene located on human chromosome 17q11.2 (chr17:31,558,803–31,560,358), has been found involved in several cancers including CRC 9–11. Besides the oncogenic role being reported only in a relatively very few studies,12 almost the vast majority of published data pointed toward a role of miR-193a-3p as tumor suppressor in both solid and blood cancers by targeting targets with potential oncogenic functions to act its tumor cell aggressive inhibiting properties 13–17. This contradiction phenomenon also could be seen in studies focused on CRC 18–20.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression

Lin

Zhang

Gao

et al. 2019

CMAR

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Background Colorectal cancer (CRC) is one of the leading causes of cancer-related death in China. Dysregulation of microRNAs (miRNAs) is involved in cancer development and progression. Our previous study showed an inverse relationship between miR-193a-3p expression and the prognosis of CRC. However, the exact biological functions of miR-193a-3p in CRC are still poorly understood. This study aimed to explore the role and mechanism of miR-193a-3p in CRC. Methods Real-time PCR and Western blotting were used to examine the expression levels of RNA and protein, respectively. A dual luciferase assay was performed to validate predicted targets of miR-193a-3p. Loss and gain-of-function studies were carried out to reveal the effects and potential mechanism of the miR-193a-3p in the proliferation, metastasis and angiogenesis of CRC cells. Results The expression levels of miR-193a-3p in human CRC cell lines were significantly decreased compared with that in normal colonic epithelium cell line. Furthermore, plasminogen activator urokinase (PLAU) was validated as a direct target gene of miR-193a-3p. Over-expression of miR-193a-3p inhibited proliferation, migration and angiogenesis of HT-29 cell, whereas forced expression of PLAU could rescue the inhibitory effects. Conclusion miR-193a-3p might inhibit CRC cell growth, migration and angiogenesis partly through targeting PLAU. MiR-193a-3p/PLAU axis might provide a potent therapeutic opportunity for aggressive CRC.

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“…For instance, they participate in extensive biological actions, including cell proliferation, invasion and apoptosis ( 18 , 20 – 23 ). Previous studies have demonstrated that miR-193a-3p is a neoplasm suppressor in various carcinomas, including hepatocellular cancer ( 24 ), gastric cancer ( 25 , 26 ), lung carcinoma ( 27 ), breast carcinoma ( 28 ) and colorectal carcinoma ( 29 , 30 ). To the best of the authors' knowledge, thus far only one study has investigated the association between miR-193a-3p and medullary thyroid carcinoma ( 31 ); however, a limitation of this study was the small sample size, which prevented a comprehensive description and analysis of TC.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑193a‑3p via targeting cyclin D1 in thyroid cancer

Wen

et al. 2020

Mol Med Rep

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Thyroid cancer (Tc) is a frequently occurring malignant tumor with a rising steadily incidence. microrna (mirna/mir)-193a-3p is an mirna that is associated with tumors, playing a crucial role in the genesis and progression of various cancers. However, the expression levels of mir-193a-3p and its molecular mechanisms in Tc remain to be elucidated. The present study aimed to probe the expression of miR-193a-3p and its clinical significance in TC, including its underlying molecular mechanisms. Microarray and rna sequencing data gathered from three major databases, specifically Gene expression omnibus (Geo), arrayexpress and The cancer Genome atlas (TcGa) databases, and the relevant data from the literature were used to examine mir-193a-3p expression. Meta-analysis was also conducted to evaluate the association between clinicopathological parameters and mir-193a-3p in 510 Tc and 59 normal samples from the TcGa database. mirWalk 3.0, and the TcGa and Geo databases were used to predict the candidate target genes of mir-193a-3p. Gene ontology, Kyoto encyclopedia of Genes and Genomes and protein-protein interaction network enrichment analyses were conducted by using the predicted candidate target genes to investigate the underlying carcinogenic mechanisms. a dual luciferase assay was performed to validate the targeting regulatory association between the most important hub gene cyclin d1 (ccnd1) and mir-193a-3p. mir-193a-3p expression was considerably downregulated in Tc compared with in the non-cancer controls (P<0.001). The area under the curve of the summary receiver operating characteristic was 0.80. Downregulation of miR-193a-3p was also significantly associated with age, sex and metastasis (P=0.020, 0.044 and 0.048, respectively). Bioinformatics analysis indicated that a low mir-193a-3p expression may augment ccnd1 expression to affect the biological processes of Tc. in addition, ccnd1, as a straightforward target, was validated through a dual luciferase assay. mir-193a-3p and ccnd1 may serve as prognostic biomarkers of Tc. Finally, mir-193a-3p may possess a crucial role in the genesis and progression of Tc by altering the ccnd1 expression.

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microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer

Cited by 30 publications

References 49 publications

<p>MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1</p>

<p>MiR-193a-3p inhibits pancreatic ductal adenocarcinoma cell proliferation by targeting CCND1</p>

<p>MicroRNA-193a-3p suppresses the colorectal cancer cell proliferation and progression through downregulating the PLAU expression</p>

Downregulation of miR‑193a‑3p via targeting cyclin D1 in thyroid cancer

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