RETRACTED: miR-539 inhibits human colorectal cancer progression by targeting RUNX2

Wen, Dacheng; Li, Songhe; Jiang, Weidong; Zhu, Jiaming; Liu, Jingjing

doi:10.1016/j.biopha.2017.09.044

Cited by 24 publications

(20 citation statements)

References 22 publications

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“…6a). KLF4 suppresses CRC cell migration and invasion [39][40][41], whereas RUNX2 and its target gene ITGBL1 are promigratory and pro-metastatic [42][43][44][45]. Similarly, overexpression of ITGA3 and ITGB7 augments migration, matrix adhesion, and metastasis formation [46,47].…”

Section: Loss Of Tcf7l2 Disturbs a Gene-regulatory Network Related Tomentioning

confidence: 99%

Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells

et al. 2020

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The transcription factor TCF7L2 is indispensable for intestinal tissue homeostasis where it transmits mitogenic Wnt/ β-Catenin signals in stem and progenitor cells, from which intestinal tumors arise. Yet, TCF7L2 belongs to the most frequently mutated genes in colorectal cancer (CRC), and tumor-suppressive functions of TCF7L2 were proposed. This apparent paradox warrants to clarify the role of TCF7L2 in colorectal carcinogenesis. Here, we investigated TCF7L2 dependence/independence of CRC cells and the cellular and molecular consequences of TCF7L2 loss-of-function. By genome editing we achieved complete TCF7L2 inactivation in several CRC cell lines without loss of viability, showing that CRC cells have widely lost the strict requirement for TCF7L2. TCF7L2 deficiency impaired G1/S progression, reminiscent of the physiological role of TCF7L2. In addition, TCF7L2-negative cells exhibited morphological changes, enhanced migration, invasion, and collagen adhesion, albeit the severity of the phenotypic alterations manifested in a cell-line-specific fashion. To provide a molecular framework for the observed cellular changes, we performed global transcriptome profiling and identified gene-regulatory networks in which TCF7L2 positively regulates the proto-oncogene MYC, while repressing the cell cycle inhibitors CDKN2C/CDKN2D. Consistent with its function in curbing cell motility and invasion, TCF7L2 directly suppresses the pro-metastatic transcription factor RUNX2 and impinges on the expression of cell adhesion molecules. Altogether, we conclude that the proliferation-stimulating activity of TCF7L2 persists in CRC cells. In addition, TCF7L2 acts as invasion suppressor. Despite its negative impact on cell cycle progression, TCF7L2 loss-of-function may thereby increase malignancy, which could explain why TCF7L2 is mutated in a sizeable fraction of colorectal tumors.

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Section: Loss Of Tcf7l2 Disturbs a Gene-regulatory Network Related Tomentioning

confidence: 99%

Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells

et al. 2020

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“…biological roles in PDAC may be advantageous to the development of miRNA-based targeted therapy, which may enhance the diagnosis, treatment and prognosis of patients with this fatal disease. miR-539 has been studied in multiple types of human cancer (17)(18)(19). However, its expression and potential biological function in PDAC remain unclear.…”

Section: Microrna-539 Inhibits Cell Proliferation Colony Formation Amentioning

confidence: 99%

“…miR-539 dysregulation has been observed in multiple types of human cancer. For example, miR-539 is downregulated in colorectal cancer tissues, and this phenomenon is associated with clinical stage and lymph node metastasis (17). The expression pattern of miR-539 is also decreased in glioma (18), oesophageal cancer (19), hepatocellular carcinoma (31,32), prostate cancer (33), nasopharyngeal carcinoma (34), osteosarcoma (35) and thyroid cancer (36).…”

Section: Recovered Igf-1r Expression Partially Counteracts the Supprementioning

confidence: 99%

“…miR-539 performs important functional roles in tumour occurrence and development. For instance, miR-539 re-expression suppresses the growth and metastasis of colorectal cancer cells in vitro and impairs tumour growth in vivo (17). Quan et al (18) found that ectopic miR-539 expression causes an evident reduction in the cell proliferation and invasion of glioma.…”

Section: Recovered Igf-1r Expression Partially Counteracts the Supprementioning

confidence: 99%

“…miRNAs can affect carcinogenesis and cancer progression by directly regulating target genes expression. Several targets identified for miR-539 thus far include RUNX2 (17) in colorectal cancer, DIXDC1 (18) in glioma, TWIST1 (19) in esophageal cancer, FSCN1 (32) in hepatocellular carcinoma, SPAG5 (33) in prostate cancer, CDK4 (34) in nasopharyngeal carcinoma, MMP8 (35) in osteosarcoma and CARMA1 (36) in thyroid cancer. In our study, IGF-1R, a transmembrane tyrosine kinase receptor, was validated as a novel target of miR-539 in PDAC.…”

Section: Recovered Igf-1r Expression Partially Counteracts the Supprementioning

confidence: 99%

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MicroRNA‑539 inhibits cell proliferation, colony formation and invasion in pancreatic ductal adenocarcinoma by directly targeting IGF‑1R

et al. 2018

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MicroRNAs (miRNAs) possess oncogenic and tumour‑suppressive roles in the carcinogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) by regulating the expression of numerous cancer‑related genes. Thus, the investigation on the expression and roles of miRNAs in PDAC may facilitate the identification of novel and effective targets for the clinical diagnosis and treatment of patients with PDAC. miRNA‑539 (miR‑539) has been studied in multiple types of human cancer. However, its expression and potential biological function in PDAC remain unclear. In the current study, the expression level, clinical significance, roles and underlying molecular mechanism of miR‑539 in PDAC. The present results demonstrated that miR‑539 expression was downregulated in PDAC tissues and cell lines. A low miR‑539 level was associated with TNM stage and lymph node metastasis of patients with PDAC. miR‑539 overexpression induced a significant reduction in the proliferation, colony formation and invasion of PDAC cells. Insulin‑like growth factor 1 receptor (IGF‑1R) was confirmed as a direct target gene of miR‑539 in PDAC. Further analysis indicated that IGF‑1R was overexpressed in PDAC tissues. Notably, the mRNA expression of IGF‑1R was negatively correlated with miR‑539 levels in PDAC tissues. In addition, the recovered IGF‑1R expression also partially counteracted the suppressive roles of miR‑539 overexpression in PDAC cells. Overall, miR‑539 may inhibit the aggressive behaviour of PDAC by directly targeting IGF‑1R and may serve as a novel therapeutic target for patients with this disease.

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Circ_0000317/microRNA‐520g/HOXD10 axis affects the biological characteristics of colorectal cancer

Lai

Xie

et al. 2021

The Kaohsiung J of Med Scie

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Circular RNAs (circRNAs) are a class of noncoding RNAs that are widely expressed in cancer tissues and play a pro-or anticancer role in modulating cancer progression. This work is aimed to probe the biological role of circ_0000317 in colorectal cancer (CRC) and its underlying mechanism. Circ_0000317 was selected from the circRNA microarray datasets (GSE121895). Quantitative real-time polymerase chain reaction was utilized to examine circ_0000317, microRNA (miR)-520g, and homeobox D10 (HOXD10) mRNA expression in CRC. Cell Counting Kit-8 and Transwell experiments were conducted to examine the effects of circ_0000317 on proliferation, migration, and invasion of CRC cells. Bioinformatic analysis and dual-luciferase reporter gene experiments were implemented to predict and validate the targeting relationship between circ_0000317 and miR-520g, miR-520g, and HOXD10. Western blot was employed to examine HOXD10 expression at protein level in CRC cells. Circ_0000317 and HOXD10 mRNA expression were unveiled to be down-modulated and miR-520g expression was upmodulated in CRC. Functionally, circ_0000317 overexpression repressed CRC cell proliferation, migration, and invasion. Mechanistically, miR-520g was a direct target of circ_0000317 and miR-520g specifically modulated HOXD10 expression. Furthermore, miR-520g mimics partially counteracted the suppressing effect of circ_0000317 on malignant phenotype of CRC cells. Circ_0000317 represses CRC progression by targeting miR-520g and modulating HOXD10 expression. Hence, circ_0000317 may be a promising diagnostic biomarker and a therapeutic target for CRC.

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RETRACTED: miR-539 inhibits human colorectal cancer progression by targeting RUNX2

Cited by 24 publications

References 22 publications

Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells

Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells

MicroRNA‑539 inhibits cell proliferation, colony formation and invasion in pancreatic ductal adenocarcinoma by directly targeting IGF‑1R

Circ_0000317/microRNA‐520g/HOXD10 axis affects the biological characteristics of colorectal cancer

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