miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ

Zhang, Xiaofei; Li, Ke‐Ke; Gao, Lu; Li, Shangze; Chen, Ke; Zhang, Junbin; Wang, Di; Tu, Rongfu; Zhang, Jinxiang; Tao, Kaixiong; Wang, Guobin; Zhang, Xiaodong

doi:10.18632/oncotarget.2864

Cited by 62 publications

(48 citation statements)

References 51 publications

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“…Many genes, such as Egr-1, C/EBPβ, Tmod2 and ChK2, have been identified as miR-191 targets [33][34][35][36]. Here we screened potential target genes of miR-191 using the TargetScan and MicroRNA.org and found sFRP1 to be a viable candidate.…”

Section: Discussionmentioning

confidence: 99%

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Kang

Leng

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. Methods: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. Results: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/β-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/β-catenin signaling pathway as detected by an increased level of β-catenin and phosphorylation of GSK-3β, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. Conclusion: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

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Section: Discussionmentioning

confidence: 99%

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

Kang

Leng

Liu

et al. 2018

Cell Physiol Biochem

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“…According to the study of Tian et al (28), miR-191-5p inhibits tumor necrosis factor-α-induced apoptosis in endometrial carcinoma cells by targeting death-associated protein kinase 1 (DAPK1). Additionally, Zhang et al (17) demonstrated that miR-191-5p promotes the tumorigenesis of colorectal cancer by targeting CCAAT-enhancer-binding protein β. Di Leva et al (29) also reported that expression of the miR-191/425 cluster reduced the proliferation and impaired tumorigenesis in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that certain miRNAs were associated with RCC carcinogenesis, upregulated miRNAs act as tumor activator whereas downregulated miRNAs act as tumor suppressors (12)(13)(14). miR-191-5p is known to be dysregulated in several tumors, including intrahepatic cholangiocarcinoma (15), breast cancer (16) and colorectal cancer (17). However, the role of miR-191-5p in RCC remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑191‑5p exerts a tumor suppressive role in renal cell carcinoma

et al. 2017

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Abstract. Renal cell carcinoma (RCC) is a common tumor of the urinary system. Previously, miR-191-5p has been reported to be associated with various types of cancer; however, its specific functions in RCC have not been investigated to date. In the present study, the expression of miR-191-5p in the 786-O and ACHN cell lines was detected in vitro by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results of RT-qPCR revealed that miR-191-5p was significantly downregulated in the two cell lines compared with the 293T cell line. miR-191-5p was also significantly downregulated in RCC tissue compared with paired normal tissue. In addition, the effects of miR-191-5p on cell proliferation, migration, invasion and apoptosis were examined by CCK-8, MTT, wound scratch, Transwell and flow cytometry assays. Downregulation of miR-191-5p was observed to promote cell proliferation, migration and invasion, as well as to repress the cell apoptosis of 786-O and ACHN cells. Therefore, the current study suggests that miR-191-5p functions as a tumor suppressor in RCC. Further studies are required to uncover the underlying signaling pathway of miR-191-5p and its potential role as a biomarker for early detection and prognosis prediction, and as a therapeutic target of RCC.

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“…In particular, 12 of the 31 identified genes have been reported in the literatures to be related to colon cancer recurrence [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], which can be regarded as validation to our prediction results for these 12 genes. For the other 19 genes identified by us, we cannot exclude the possibility that some of them are due to false positive prediction.…”

Section: Discussionmentioning

confidence: 54%

Exploration of immunogene in colon cancer recurrence

Sun¹,

Yao²,

Yuan³

et al. 2018

Oncotarget

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Colon adenocarcinoma is the third most common cancer with high risk of recurrence and deteriorative consequences. Given the importance of immune genes in tumor regulation and cancer immunotherapy, there is a need to comprehensively profile the immunoregulatory genes from multiple types of colon cancer patient genomic data for discovering important associations and potential therapeutic targets of colon cancer recurrence. We used publicly available colon tumor tissue genomic data from The Cancer Genome Atlas database and immune genes data from innateDB database in this study. We derived the immune genes profiles by exploring multiple genomic profiles (gene expression, clinical and somatic mutation) in colon cancer. Some of the synthetic lethal genes we identified, such as CASP14, MS4A6E, KIR2DL1, KIR3DL1, KIR2DL3, CCL1, IL36B, FOXO3, POU2F1, SMAD3, HOXA9, PACS1, PROM1, DIDO1, SRC, CBFA2T2, NCOA6, PGAM1 and PROC, have been suggested to be potential targets correlated with immune genes for colon cancer recurrence treatment. Moreover, TLR2 could be promisingly new early stage indicator for colon adenocarcinoma recurrence. This is a systematic study that combines three different types of genomic data to molecularly characterize colon cancer and aims to identify potential targets for colon adenocarcinoma therapy. Meanwhile, the integrative analysis of immune genes for colon cancer could assist in identifying potential new symbols for colon adenocarcinoma recurrence.

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miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ

Cited by 62 publications

References 51 publications

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma

MicroRNA‑191‑5p exerts a tumor suppressive role in renal cell carcinoma

Exploration of immunogene in colon cancer recurrence

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