miR-132 inhibits colorectal cancer invasion and metastasis<i>via</i>directly targeting ZEB2

Zheng, Yongbin; Luo, Hai-Ping; Shi, Qiang; Hao, Zhi-Nan; Ding, Yu; Wang, Qiushuang; Li, Shengbo; Xiao, Gaochun; Tong, Shilun

doi:10.3748/wjg.v20.i21.6515

Cited by 101 publications

(93 citation statements)

References 26 publications

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“…High ZEB2 expression was found in diverse types of cancers including pancreatic cancer (Imamichi et al, 2007;Usova et al, 2013;Lee et al, 2014;You et al, 2014). Intriguingly, several miRs, such as miR-132 (Zheng et al, 2014), miR-144 (Guan et al, 2014), and miR-200c , participate in the regulation of the activity of ZEB2 in different tissues, but the potential regulatory effect of miR-215 on ZEB2 expression in pancreatic cancer has not been confirmed.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

Qw¹,

Zhou²,

F³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. It has been shown that microRNA-215 (miR-215) is dysregulated in several human malignancies, and this correlates with tumor progression. However, its expression and function in pancreatic cancer is still unclear. The aim of this study was to explore the effects of miR-215 on pancreatic cancer formation and progression. Using quantitative RT-PCR, we detected miR-215 expression in pancreatic cancer cell lines and primary tumor tissues. The association of miR-215 expression with clinicopathological factors and prognosis was also analyzed. We then observed the effects of miR-215 on the biological behavior of pancreatic cancer cells. Lastly, the potential regulatory function of miR-215 on ZEB2 expression was investigated. miR-215 expression levels were significantly downregulated in pancreatic cancer samples and cell lines. Decreased miR-215 expression was significantly associated with large tumor size, advanced TNM stage, lymph node metastasis, vessel invasion, and lower overall survival. Multivariate regression analysis corroborated that downregulation of miR-215 was an independent unfavorable prognostic factor. Overexpression of miR-215 inhibited pancreatic cancer cell 16133-16145 (2015) proliferation, invasion, and migration; promoted cell apoptosis in vitro; and suppressed tumorigenicity in vivo. Further, ZEB2 was confirmed as a direct target of miR-215 by using a luciferase reporter assay. These findings indicate that miR-215 may act as a tumor suppressor in pancreatic cancer cells, and could serve as a novel therapeutic target for miR-based therapy.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

Qw¹,

Zhou²,

F³

et al. 2015

Genet. Mol. Res.

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“…Similar scenario is reported in case of miRNA. Thus, anti-onco miR-132 or -133b rather increased in tumor tissues (28)(29)(30). In addition, some reports showed that miR-34a, a representative anti-oncomir (31,32), was shown to be upregulated in cancer tissue rather than in normal mucosa (30,33).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Hata

Mokutani

Takahashi

et al. 2016

International Journal of Oncology

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Abstract.Recent studies have shown that microRNAs (miRNAs) are involved in the progression of colorectal cancer (CRC). The aim of this study is to identify a novel miRNA that especially relates to liver metastasis and to explore the underlying mechanism. Differentially expressed miRNAs were analyzed using microarray, in primary CRC tumors without metastasis (n=16), those with liver metastasis (n=12), and liver metastatic lesions (n=8). We found that miR-487b level decreased in liver metastatic lesions, and qRT-PCR confirmed the results in the validating cohort (n=134). Survival analysis indicated that high expression of miR-487b was associated with better prognosis. In vitro studies were also performed to investigate the functional significance of miR-487b in human CRC cell lines. miR-487b showed an inhibitory effect on cell proliferation and invasion of CRC cells. miR-487b downregulated KRAS and inhibited its downstream signal pathways, and the luciferase reporter assay revealed that miR-487b directly targeted LRP6, a receptor for WNT/β-catenin signaling. These findings showed that decrease in miR-487b was related with liver metastasis. Our data suggest a possibility that miR-487b may suppress metastasis of CRC progression through inhibition of KRAS.

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“…Another previous study had reported that miR-132 could inhibit CRC cell invasion and epithelialmesenchymal transition (EMT) via targeting ZEB2, an EMT regulator [11]. Nevertheless, the expression and inhibitory roles of miR-132 in CRC cells were far from been clearly understood.…”

Section: Cck-8 Assaymentioning

confidence: 99%

“…After confirming the decreased level of miR-132 in CRC tissues and cell lines, we mainly focused on the roles of miR-132 in RKO cell proliferation and apoptosis, because Zhang et al had already reported that miR-132 could impact on CRC cell invasion and metastasis [11]. MiR-132 was forced expressed in RKO cells (Figure 2A) and 48 h later, CCK-8 assay was performed to evaluate the cell proliferation rate by miR-132 overexpression compared with the scramble sequences transfection group.…”

Section: Mir-132 Inhibited Cell Proliferation and Promoted Apoptosis mentioning

confidence: 99%

Decreased expression of miR-132 in CRC tissues and its inhibitory function on tumor progression

Chen

Han

et al. 2016

Open Life Sciences

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Objectives Colorectal cancer (CRC) is among the most common types of malignancies in the worldwide, and microRNAs (miRNAs) emerge as key regulators in carcinogenesis and tumor progression. Here we intended to address the expression and function of miR-132 in CRC cells. Methods Paired CRC tissues and several established cell lines were firstly collected. We performed qPCR to detect the expression of miR-132 in these tissues and cell lines. Cell proliferation and apoptosis were respectively monitored by CCK-8 assay and Annexin-V/PI staining followed by flow cytometry, after miR-132 was transiently overexpressed in RKO cells. Afterwards, Luciferase reporter assays were performed to examine the targeting of YAP1 by miR-132. Finally, qPCR and western blotting were also carried out to validate this targeting. Results MiR-132 was significantly decreased in CRC and its overexpression in RKO cells exerted tumor suppressing effects, including cell growth arrest and apoptosis promotion. Additionally, we proved that miR-132 could negatively regulate the expression of YAP1. Conclusion Our findings suggested that miR-132 was downregulated in CRC, and played as a tumor suppressor to inhibit cell proliferation and induce apoptosis. And these anti-tumor activities might be related with the targeting of YAP1 by miR-132.

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miR-132 inhibits colorectal cancer invasion and metastasisviadirectly targeting ZEB2

Abstract: Our study indicated that miR-132 plays an important role in the invasion and metastasis of CRC.

Cited by 101 publications

References 26 publications

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Decreased expression of miR-132 in CRC tissues and its inhibitory function on tumor progression

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