The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

Hou, Qiang; Han, Shuxian; Yang, Lin; Chen, Shengwen; Chen, Junxiu; Ma, Nan; Wang, Chao; Tang, Junhua; Chen, Xiaogang; Chen, Feng; Dong, Xiang Da; Tu, Lili

doi:10.1167/iovs.18-26477

Cited by 27 publications

(18 citation statements)

References 44 publications

(58 reference statements)

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“…Transfection of miR-34a/b/c resulted in target protein downregulation and reduction in cell proliferation, invasion and migration [50,96]. Follow-on studies of miR-34a have reported its involvement in the regulation of LGR4, a universal tumour promoter, and downstream epithelial-to-mesenchymal transition proteins such as E-cadherin, N-cadherin, vimentin, SNAIL and MMP2 [97], such that downregulation of miR-34a lends to activation of epithelial signalling [97].…”

Section: Mirna As Tumour Suppressors In Ummentioning

confidence: 99%

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

Aughton

Kalirai

Coupland

2020

IJMS

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Uveal melanoma (UM) is a rare tumour of the eye, characterised by a high propensity to metastasise in half of all patients, most frequently to the liver. Although there are effective treatment options for the primary tumour, once metastasis has occurred prognosis is poor, with overall survival limited to months. Currently, there are no effective treatments for metastatic UM, despite the tumour having a well-defined signalling pathway to which many therapies have been directed. In an effort to develop novel treatment approaches, understanding the role of other signalling molecules, such as microRNAs, is fundamental. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in posttranscriptional gene regulation, resulting in reduced target gene expression and subsequent protein translation. In UM, several dysregulated miRNAs have been proposed to play a functional role in disease progression, whereas others have been put forward as clinical biomarkers of high-risk disease following isolation from blood, plasma and exosomes. Most recently, analyses of large datasets have identified promising prognostic miRNA signatures and panels. This review navigates the plethora of aberrant miRNAs disclosed so far in UM, and maps these to signalling pathways, which could be targeted in future therapies for the disseminated disease.

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Section: Mirna As Tumour Suppressors In Ummentioning

confidence: 99%

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

Aughton

Kalirai

Coupland

2020

IJMS

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“…The EMT signaling pathway is further complicated by interactions with matrix metalloproteinases. Among these complex interactions, MMP2 and other MMPs have been demonstrated to promote EMT, which is involved in cancer invasion (43,44). The present study revealed that increased miR-30a-5p expression following curcumol treatment inhibited CRC cell invasion, migration and MMP2 expression, and activated the Hippo signaling pathway.…”

Section: Discussionmentioning

confidence: 50%

Curcumol inhibits the viability and invasion of colorectal cancer cells via miR‑30a‑5p and Hippo signaling pathway

Qin

et al. 2021

Oncol Lett

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MicroRNA-30a-5p (miR-30a-5p), which functions as a tumor suppressor, has been reported to be downregulated in colorectal cancer (CRC) tissues and to be associated with cancer invasion. However, the detailed regulatory mechanism of curcumol in the malignant progression of CRC remains unknown. MTT, Transwell, scratch, western blotting and reverse transcription-quantitative PCR assays were performed to examine how curcumol inhibited CRC cell viability, invasion and migration, and to detect the role of miR-30a-5p and curcumol in the invasion and Hippo signaling pathways of CRC cells. The present study revealed that miR-30a-5p expression was downregulated in human CRC tissues and cells. The results demonstrated that miR-30a-5p downregulation was accompanied by the inactivation of the Hippo signaling pathway, which was demonstrated to promote CRC cell viability, invasion and migration. Curcumol treatment was identified to increase miR-30a-5p expression and to activate the Hippo signaling pathway, which in turn inhibited the invasion and migration of CRC cells. Overexpression of miR-30a-5p enhanced the effects of curcumol on cell invasion and migration, and the Hippo signaling pathway in CRC cells. Furthermore, downregulation of miR-30a-5p reversed the effects of curcumol on cell invasion and migration, and the Hippo signaling pathway in CRC cells. These findings identified novel signaling pathways associated with miR-30a-5p and revealed the effects of curcumol on miR-30a-5p expression. Therefore, curcumol may serve as a potential therapeutic strategy to delay CRC progression.

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“…For example, KAI1 can suppress the progression of cancers of the digestive system via influencing invasion-associated protein metabolism (41). It also serves as an important tumor suppressor gene in the context of integumental tumors, with KAI1 inactivating mutations being a common feature in human melanoma (42). The ability of KAI1 to suppress oncogenesis is linked to its ability to inhibit the expression of AP-1, JUNB, poly (ADP-ribose) polymerase (PARP) and other oncogenes (43).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑633 enhances melanoma cell proliferation and migration by suppressing KAI1

Wang

Liu

2020

Oncol Lett

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The aim of the present study was to determine the impact of microRNA (miRNA/miR)-633 on the biological properties of malignant melanoma cells. Kang-Ai 1 (KAI1), also known as cluster of differentiation 82, is an important transcriptional regulator and tumor suppressor gene present in different types of tumors. miRNAs that potentially bind with KAI1 were predicted via bioinformatics analyses. In total, six putative miRNA regulators of KAI1 were identified in the present analysis, among which miR-633 was upregulated the most in melanoma tissues compared with the control group. The expression levels of miR-633 and KAI1 in melanoma tissues compared with adjacent normal tissues were then assessed. It was found that miR-633 was significantly upregulated in melanoma cells compared with the control group, whereas the expression levels of KAI1 showed the opposite results. miR-633 was predicted to target the 3′-untranslated region of KAI1 using predictive online tools, and results from luciferase reporter assays confirmed the direct regulation of KAI1 promoter activity by miR-633. Furthermore, miR-633 mimics over expression was shown to suppress both mRNA and protein expression of KAI1, while miR-633 inhibition resulted in decreased viability and migrationin melanoma cells in vitro . Taken together, the present study demonstrated, to the best of the authors' knowledge for the first time, that miR-633 exerts an important role in melanoma through targeting KAI1.

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The Interplay of MicroRNA-34a, LGR4, EMT-Associated Factors, and MMP2 in Regulating Uveal Melanoma Cells

Cited by 27 publications

References 44 publications

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

MicroRNAs and Uveal Melanoma: Understanding the Diverse Role of These Small Molecular Regulators

Curcumol inhibits the viability and invasion of colorectal cancer cells via miR‑30a‑5p and Hippo signaling pathway

MicroRNA‑633 enhances melanoma cell proliferation and migration by suppressing KAI1

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