miR‐9: From function to therapeutic potential in cancer

Khafaei, Mostafa; Rezaie, Ehsan; Mohammadi, Ali; Gerdehsang, Payam Shahnazi; Ghavidel, Sara; Kadkhoda, Sepideh; Zahra, Atieh Zorrieh; Forouzanfar, Narjes; Arabameri, Hossein; Tavallaie, Mahmood

doi:10.1002/jcp.28210

Cited by 38 publications

(34 citation statements)

References 117 publications

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“…Several miRNAs that are overexpressed in ACC relative to NAC have proven oncogenic roles in vitro, as well as defined molecular targets, that they regulate (Table 3). miR-9 [104], miR-21 [105], miR-483-3p [106], and miR-483-5p [106] have been well described in the literature as 'oncomiRs' across multiple mammalian cell types, which is consistent with their role in ACC. In contrast, miR-139-5p is an established tumor suppressor in head and neck/oral, breast, and gastric cancers [107], but is overexpressed in aggressive ACCs compared with non-aggressive ACCs [108].…”

Section: Overexpressed Mirnas and Their Accssupporting

confidence: 56%

Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Chehade

Bullock

Glover

et al. 2020

Cancers

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Adrenocortical Carcinoma (ACC) is a rare but aggressive malignancy with poor prognosis and limited response to available systemic therapies. Although complete surgical resection gives the best chance for long-term survival, ACC has a two-year recurrence rate of 50%, which poses a therapeutic challenge. High throughput analyses focused on characterizing the molecular signature of ACC have revealed specific micro-RNAs (miRNAs) that are associated with aggressive tumor phenotypes. MiRNAs are small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation or degrading mRNA transcripts and have been generally implicated in carcinogenesis. This review summarizes the current insights into dysregulated miRNAs in ACC tumorigenesis, their known functions, and specific targetomes. In addition, we explore the possibility of particular miRNAs to be exploited as clinical biomarkers in ACC and as potential therapeutics.

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Section: Overexpressed Mirnas and Their Accssupporting

confidence: 56%

Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Chehade

Bullock

Glover

et al. 2020

Cancers

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“…Clinical and experimental studies using miRNAs have gained much interest to understand the pathogenesis and explore miRNAs as therapeutic targets [19]. Although miR-9 was first reported as a pro-inflammatory signal regulator [20], recent studies have demonstrated its potential in malignant diseases [21]. Increased expression of miR-9 in OS tissues compared with non-cancerous bone tissues has been observed.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-9 decreases osteosarcoma cell proliferation

Wei

Huang

et al. 2019

Bosn J of Basic Med Sci

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Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. Small interfering RNA against miR-9 and miR-9 mimics were used to study the function of miR-9 in these two cell lines. We determined the effect of miR-9 inhibition on cell proliferation, cell cycle, apoptosis, and the protein expression of different genes. Our results demonstrated that miR-9 knockdown in the human OS cell lines inhibits their metastatic potential, as determined by decreased cell proliferation and cell cycle arrest, decreased invasion, and increased apoptosis. The western blot analysis showed that cadherin-1 (CDH1), matrix metalloproteinase 13 (MMP-13), forkhead box O3 (FOXO3a), Bcl-2-like protein 11 (BCL2L11), and β-catenin (CTNNB1) are involved in miR-9 signaling. Moreover, miR-9 mimics rescued the effects caused by the inhibition of miR-9 in the OS cell lines. Our findings suggest that miR-9 is important for mediating OS cell migration, invasion, metastasis, and apoptosis. Inhibition of miR-9 could be further explored as a therapeutic target to treat OS.

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“…There are studies which mentioned miR-451a as pro-apoptotic which inhibits aggressiveness features in squamous lung cancer [41], miR-107 regulates proliferation and migration in OSCC [42], miR-184 associated to proliferation and Cisplatin resistance in OSCC [43] miR-221-3p/miR-222 belongs to same class and were enriched in positive regulation of protein localization to telomere and telomere maintenance via telomerase which is very important pathway for cancer pathogenesis. Various studies have shown that overexpression of miR-221-3p/222-3p increases growth and tumorigenesis in OSCC [44] but their significance to OPMDs are not mentioned to the best of our knowledge.miR-9 was selected in this study due to its controversial expression profile in many cancer types such as down regulated in Breast cancer,Renal cell carcinoma, gastric cell carcinoma and HNSCC) on the other hand is found to be up-regulated in hepatocellular, gliomas and colorectal cancers [45]. In a study by Kim et al, compression induced miR-9 downregulation and reversal was seen in breast cancer tissues [46],this suggest that mechanotransduction is followed in miR-9 which may be associated to OSF also, therefore we decided to explore miR-9 in OSCC and OSF tissues.…”

Section: String Network and Molecular Function Analysesmentioning

confidence: 99%

In-silico, interactomic and clinical validation based approach for screening and identification of miR biomarkers involved in Oral submucous fibrosis to Oral squamous cell carcinoma transition

Ukey

Vishnoi

Choudhury

et al. 2020

Preprint

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Oral Squamous Cell Carcinoma (OSCC) is common preventable disease when diagnosed early, but mostly its progression follows transition from oral potentially malignant disorders (OPMDs) like Oral Submucous Fibrosis (OSF). However, it is difficult to predict possibilities of progression in these premalignant lesions hence, identification of molecular biomarkers would have major clinical impact in early diagnosis and better prognosis. In this context microRNAs(miRs) provide better opportunities in malignancy prediction and demarcation in OSF to OSCC transition as they perform key regulatory roles in many tumorigenic processes. Here, we computationally screened differentially expressed miRs of OSCC and OSF from public databases followed by construction of protein interaction networks and enrichment analyses. The relevant miRs were validated using qPCR of total 93 samplesincluding 34 OSCC, 30 OSF and 29 control blood and tissue samples. We identified significant down regulation of miR-133a-3p in OSCC compared to controls and interesting up-regulation compared to OSCC and control. miR-9-5p was up-regulated in OSF as well as OSCC and down-regulated in OSF compared to OSCC. Therefore, these two miRs may serve as risk stratification biomarkers with validation in larger categorical datasets.

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miR‐9: From function to therapeutic potential in cancer

Cited by 38 publications

References 117 publications

Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Inhibition of miR-9 decreases osteosarcoma cell proliferation

In-silico, interactomic and clinical validation based approach for screening and identification of miR biomarkers involved in Oral submucous fibrosis to Oral squamous cell carcinoma transition

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