MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer

Gb, Xiong; Gn, Zhang; Xiao, Yuanxun; Bz, Niu; Hz, Qiu; Wu, Bingcheng; Gl, Lin; Li, You; Hu, Shu

doi:10.4149/neo_2015_104

Cited by 14 publications

(11 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Huang et al (29) reported that the expression level of miR-219 was reduced in papillary thyroid carcinoma tissues, and low miR-219 expression was associated with sex, tumor size, and lymph node metastasis in patients with papillary thyroid carcinoma. Xiong et al (30) observed that miR-219 was lower in colorectal cancer tissues when compared with corresponding matched normal tissues. In addition, downregulation of miR-219 has been reported in medulloblastoma (31), tongue squamous cells carcinoma (32) and colon cancer (33).…”

Section: Discussionmentioning

confidence: 99%

“…Shi et al (31) demonstrated that upregulation of miR-219 inhibited the proliferation, migration and invasion of medulloblastoma cells, with CD164 as a direct target. In addition, miR-219 was demonstrated to repress the proliferation of colorectal cancer cells, as well as promote apoptosis and induce cell cycle arrest at the G 1 phase via inhibition of platelet-derived growth factor receptor α (30). Furthermore, Cheng et al (33) revealed that miR-219 decreased the proliferation, migration and invasion of colon cancer cells, as well as reduced drug resistance and induced apoptosis via downregulation of spalt like transcription factor 4.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-219 is downregulated in non-small cell lung cancer and inhibits cell growth and metastasis by targeting HMGA2

Sun

Liu

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, and accounts for ~85% of all lung cancer cases. An increasing number of studies suggest that microRNAs (miRs) may be involved in the regulation of NSCLC carcinogenesis and progression. However, the expression and function of miRNA-219 in NSCLC, and its underlying mechanisms of action, remain unknown. In the present study, miR-219 expression in NSCLC tissues and cell lines was determined using reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-219 mimics, the effects of miR-219 overexpression on NSCLC cell proliferation, migration and invasion were examined. Furthermore, the miR-219 target in NSCLC was investigated. miR-219 was observed to be downregulated in NSCLC tissues and NSCLC cell lines. In addition, miR-219 was demonstrated to function as a tumor suppressor in NSCLC, through inhibiting cell proliferation, migration and invasion in vitro. Furthermore, high mobility group AT-hook 2 (HMGA2) was identified to be a direct target of miR-219 in NSCLC, and downregulation of HMGA2 suppressed NSCLC cell proliferation, migration and invasion in vitro. HMGA2 expression was upregulated in NSCLC tissues, and was inversely correlated with miR-219 expression. In conclusion, miR-219 functions as a tumor suppressor and may be important in inhibiting the growth and metastasis of NSCLC cells via directly targeting HMGA2. Therefore, miR-219 may present a potential novel therapeutic target for NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-219 is downregulated in non-small cell lung cancer and inhibits cell growth and metastasis by targeting HMGA2

Sun

Liu

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Several studies have indicated that aberrant expression of miRs, such as miR‐21, miR‐let‐7 and miR‐24, is associated with proliferation, apoptosis, and invasion of CRC cells by targeting corresponding function proteins . As for miR‐219‐5p, it has been reported as a tumor suppressor in gastric cancer, glioblastoma and esophageal adenocarcinoma, and it also works as a negative regulator of cell proliferation in CRC by targeting platelet‐derived growth factor receptor . However, the mechanism between miR‐219‐5p and metastasis of CRC remains unclear.…”

mentioning

confidence: 99%

“…(5) As for miR-219-5p, it has been reported as a tumor suppressor in gastric cancer, glioblastoma and esophageal adenocarcinoma, (6)(7)(8) and it also works as a negative regulator of cell proliferation in CRC by targeting platelet-derived growth factor receptor. (9) However, the mechanism between miR-219-5p and metastasis of CRC remains unclear.…”

mentioning

confidence: 99%

microRNA‐219‐5p inhibits epithelial‐mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer‐binding factor 1

Huang

et al. 2017

Cancer Science

View full text Add to dashboard Cite

Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. microRNA‐219‐5p (miR‐219‐5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR‐219‐5p and colorectal cancer (CRC) metastasis remains unclear. In the present study, miR‐219‐5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer‐binding factor 1 (LEF1) as a direct target of miR‐219‐5p. Overexpression of miR‐219‐5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial‐mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis‐suppressive function. The recovery experiment showed that re‐expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR‐219‐5p. Additionally, we demonstrated that miR‐219‐5p exerted this tumor‐suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR‐219‐5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR‐219‐5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.

show abstract

“…However, the state-of-the-art technology for modeling human cancers in vivo is the CRISPR-Cas9 system, which in a recent study was successfully used to knock-out miR-219 and miR-315 in D. melanogaster 168 . Although the roles of miR-219 and miR-315 were not evaluated biochemically in the mutant flies, other investigations have reported that miR-219 is an essential neurodifferentiation factor 175–177 , and is suppressed in several human cancers, of which the reduced expression ultimately drives the acquisition of tumorigenic properties via diverse mechanisms 178–181 . Regardless, this pioneering study was the first to highlight the power of the CRISPR-Cas9 technology in developing transgenic D. melanogaster models to study miRNA lof , which will likely lead to new and innovative miRNA functional studies.…”

Section: Generation Of Model Organisms and Their Use In Mirna Funcmentioning

confidence: 99%

Animal Models to Study MicroRNA Function

Pal

Kasinski

2017

Advances in Cancer Research

View full text Add to dashboard Cite

The discovery of the microRNAs, lin-4 and let-7 as critical mediators of normal development in Caenorhabditis elegans and their conservation throughout evolution has spearheaded research towards identifying novel roles of microRNAs in other cellular processes. To accurately elucidate these fundamental functions, especially in the context of an intact organism various microRNA transgenic models have been generated and evaluated. Transgenic C. elegans (worms), Drosophila melanogaster (flies), Danio rerio (zebrafish), and Mus musculus (mouse) have contributed immensely towards uncovering the roles of multiple microRNAs in cellular processes such as proliferation, differentiation, and apoptosis, pathways that are severely altered in human diseases such as cancer. The simple model organisms, C. elegans, D. melanogaster and D. rerio do not develop cancers, but have proved to be convenient systesm in microRNA research, especially in characterizing the microRNA biogenesis machinery which is often dysregulated during human tumorigenesis. The microRNA-dependent events delineated via these simple in vivo systems have been further verified in vitro, and in more complex models of cancers, such as M. musculus. The focus of this review is to provide an overview of the important contributions made in the microRNA field using model organisms. The simple model systems provided the basis for the importance of microRNAs in normal cellular physiology, while the more complex animal systems provided evidence for the role of microRNAs dysregulation in cancers. Highlights include an overview of the various strategies used to generate transgenic organisms and a review of the use of transgenic mice for evaluating pre-clinical efficacy of microRNA-based cancer therapeutics.

show abstract

MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer

Cited by 14 publications

References 45 publications

MicroRNA-219 is downregulated in non-small cell lung cancer and inhibits cell growth and metastasis by targeting HMGA2

MicroRNA-219 is downregulated in non-small cell lung cancer and inhibits cell growth and metastasis by targeting HMGA2

microRNA‐219‐5p inhibits epithelial‐mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer‐binding factor 1

Animal Models to Study MicroRNA Function

Contact Info

Product

Resources

About