The Dual Role of miR-186 in Cancers: Oncomir Battling With Tumor Suppressor miRNA

Xiang, Ying; Tian, Qing; Guan, Li; Niu, Sheng

doi:10.3389/fonc.2020.00233

Cited by 35 publications

(36 citation statements)

References 84 publications

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“…miR-186 is a well-studied molecule that presented either high-expression or low-expression profiles, and played either tumor-inhibiting or oncogenic roles in different human cancer types. 11,24 In most cases, miR-186 was said to be downregulated in cancers and to inhibit cancer development including GC. 24 This was in line with our current findings which suggested decreased expression of miR-186 in GC cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…11,24 In most cases, miR-186 was said to be downregulated in cancers and to inhibit cancer development including GC. 24 This was in line with our current findings which suggested decreased expression of miR-186 in GC cell lines. Thereafter, miR-186 mimic was introduced in these cell lines, after which the proliferation, invasion, as well as resistance to apoptosis of the GC cells were decreased.…”

Section: Discussionmentioning

confidence: 99%

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<p>CREB1 Suppresses Transcription of microRNA-186 to Promote Growth, Invasion and Epithelial–Mesenchymal Transition of Gastric Cancer Cells Through the KRT8/HIF-1α Axis</p>

Huang

Liu

Jiang

et al. 2020

CMAR

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Background: The cAMP response element-binding protein 1 (CREB1) was initiated as a potential target for cancer treatment. This research was conducted to probe the effect of CREB1 in the progression of gastric cancer (GC) and the molecules involved. Materials and Methods: CREB1 expression in GC tissues and cell lines (AGS and MKN-45) as well as that in normal tissues and in gastric mucosa cell line (GES-1) was detected. The correlation between CREB1 expression and prognosis of GC patients was determined. Artificial silencing of CREB1 was introduced to evaluate its effect on biological behaviors of GC cells. The target microRNA (miRNA) of CREB1 and the target mRNA of miR-186 were predicted and validated. Altered expression of miR-186, KRT8 and HIF-1α was introduced to confirm their functions in GC progression. Results: CREB1 was abundantly expressed in GC tissues and cells and linked to dismal prognosis in patients. Silencing of CREB1 or upregulation of miR-186 suppressed the malignant behaviors such as growth, epithelial-mesenchymal transition (EMT) and invasion of GC cells, while artificial overexpression of KRT8 led to reversed trends. KRT8 was a target mRNA of miR-186, and CREB1 transcriptionally suppressed miR-186 expression to further up-regulate KRT8. KRT8 was also found to increase HIF-1α expression. Upregulation of HIF-1α was found to block the suppressing role of CREB1 silencing in GC cell malignancy. Conclusion: This study evidenced that silencing of CREB1 inhibits growth, invasion, EMT and resistance to apoptosis of GC cells involving the upregulation of miR-186 and the following downregulation of KRT8 and HIF-1α.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>CREB1 Suppresses Transcription of microRNA-186 to Promote Growth, Invasion and Epithelial–Mesenchymal Transition of Gastric Cancer Cells Through the KRT8/HIF-1α Axis</p>

Huang

Liu

Jiang

et al. 2020

CMAR

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“…However, some miRNAs are often cancer specific, whereby the miRNA is overexpressed in a specific type of tumor but is suppressed in other types of cancer (54). Dysregulated expression of miRNAs is associated with increased cancer incidence, which are considered oncomiRs or anti-oncomiRs (48). Downregulated or upregulated expression of miRNAs can regulate carcinogenesis and affect cell proliferation by interfering with cell cycle regulators (48).…”

Section: Expression Of Mirnas In Cancermentioning

confidence: 99%

“…Cancer is a complex, multifactorial disease characterized by uncontrolled proliferation of abnormal cells, mainly due to oncogenes or tumor suppressor genes ( 48 ). Recent studies have highlighted the importance of miRNAs in the development and progression of cancer, and deregulated miRNA expression has been observed in different types of cancer, including hepatocellular carcinoma, gastric cancer and colorectal cancer ( 9 , 13 ).…”

Section: Expression Of Mirnas In Cancermentioning

confidence: 99%

“…Recent studies have highlighted the importance of miRNAs in the development and progression of cancer, and deregulated miRNA expression has been observed in different types of cancer, including hepatocellular carcinoma, gastric cancer and colorectal cancer ( 9 , 13 ). A significant association has been reported between miRNAs and cancer incidence ( 48 ). miRNAs bind to their target oncogene or tumor suppressor gene ( 13 ).…”

Section: Expression Of Mirnas In Cancermentioning

confidence: 99%

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Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

et al. 2021

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Tumor-associated inflammation and aberrantly expressed biomarkers have been demonstrated to play crucial roles in the cancer microenvironment. Cyclooxygenase-2 (COX-2), a prominent inflammatory factor, is highly expressed in tumor cells and contributes to tumor growth, recurrence and metastasis. Overexpression of COX-2 may occur at both transcriptional and post-transcriptional levels. Thus, an improved understanding of the regulatory mechanisms of COX-2 can facilitate the development of novel antitumor therapies. MicroRNAs (miRNAs) are a group of small non-coding RNAs that act as translation repressors of target mRNAs, and play vital roles in regulating cancer development and progression. The present review discusses the association between miRNAs and COX-2 expression in different types of cancer. Understanding the regulatory role of miRNAs in COX-2 post-transcription can provide novel insight for suppressing COX-2 expression via gene silencing mechanisms, which offer new perspectives and future directions for the development of novel COX-2 selective inhibitors based on miRNAs. Contents 1. Introduction 2. Roles of COX-2 in cancer 3. Expression of miRNAs in cancer 4. Post-transcriptional COX-2 regulation is mediated by miRNAs 5. Upregulated expression of miRNAs by COX-2 selective inhibitor 6. Conclusions

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Identification and characterization of novel CD274 (PD‐L1) regulating microRNAs and their functional relevance in melanoma

Vaxevanis

Friedrich

Tretbar

et al. 2022

Clinical & Translational Med

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Background Immune checkpoint inhibitors directed against programmed cell death 1 (PDCD1/PD1) receptor and programmed cell death‐ligand 1 (CD274/PD‐L1) have been recently successfully implemented for the treatment of many cancers, but the response rate of tumour patients is still limited due to intrinsic and acquired resistances. However, the underlying molecular mechanisms of this limited response have still to be defined in detail. The aim of this study is to uncover processes inhibiting PDCD1/CD274 expression thereby enhancing anti‐tumour immune responses. The identification and characterization of microRNAs (miRNAs) targeting the 3′‐untranslated region (3′‐UTR) as well as the coding sequence (CDS) of CD274 will provide the basis for a new drug development. Methods Human melanoma cell lines and tissue samples were subjected to mRNA and/or protein expression analysis using qPCR, Western blot, flow cytometry, and/or immunohistochemistry. The data were correlated to clinical parameters. MiRNA trapping by RNA in vitro affinity purification (miTRAP) technology in combination with small RNA sequencing and different bioinformatics tools were employed to identify CD274‐regulating miRNAs. Results Screening based on miTRAP in combination with RNAseq identified a large number of novel CD274‐regulating candidate miRNAs, from which eight selected miRNAs were functionally validated. Five out of eight miRNAs were able to significantly reduce CD274 surface expression indicating that these miRNAs directly bind to the 3′‐UTR or CDS of the CD274 gene. The miRNA‐mediated inhibition of CD274 expression was accompanied by an increased T cell recognition. Furthermore, an inverse expression of three CD274‐regulating miRNAs and CD274 was demonstrated in melanoma lesions. A CD274 miRNA score was generated, which was associated with disease progression and reduced survival of melanoma patients. Conclusions These data revealed a novel mechanism that miRNAs targeting the CDS of immune checkpoint genes are functional, have prognostic relevance, and also the potential for the development of novel miRNA‐based therapies.

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The Dual Role of miR-186 in Cancers: Oncomir Battling With Tumor Suppressor miRNA

Cited by 35 publications

References 84 publications

<p>CREB1 Suppresses Transcription of microRNA-186 to Promote Growth, Invasion and Epithelial–Mesenchymal Transition of Gastric Cancer Cells Through the KRT8/HIF-1α Axis</p>

<p>CREB1 Suppresses Transcription of microRNA-186 to Promote Growth, Invasion and Epithelial–Mesenchymal Transition of Gastric Cancer Cells Through the KRT8/HIF-1α Axis</p>

Interplay between cyclooxygenase‑2 and microRNAs in cancer (Review)

Identification and characterization of novel CD274 (PD‐L1) regulating microRNAs and their functional relevance in melanoma

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