MiR-148a, a microRNA upregulated in the WNT subgroup tumors, inhibits invasion and tumorigenic potential of medulloblastoma cells by targeting Neuropilin 1

Yogi, Kedar; Epari, Sridhar; Goel, Naina; Jalali, Rakesh; Goel, Atul; Moiyadi, Aliasgar; Thorat, Rahul; Panwalkar, Pooja; Khire, Atul; Dasgupta, Archya; Shetty, Prakash; Shirsat, Neelam

doi:10.18632/oncoscience.137

Cited by 31 publications

(33 citation statements)

References 45 publications

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“…Cao et al showed also that the knockdown of NRP-1 by short hairpin RNA reduced migration and invasion of renal carcinoma cells [ 13 ] which was also found in our results with a decrease of invasion ability of MB stem cells after exposure to MR438. In the same way, it was recently shown that MiR-148a, a MiRNA which decreased NRP-1 expression, also inhibited invasion and tumorigenic potential of MB cells in the WNT subgroup [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1

et al. 2018

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Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains important. The neuropilin-1 (NRP-1) receptor has recently been implicated in tumor progression of MB, which seems to play an important role in the phenotype of cancer stem cells. Targeting this receptor appears as an interesting strategy to promote MB stem cells differentiation. Cancer stem-like cells of 3 MB cell lines (DAOY, D283-Med and D341-Med), classified in the more pejorative molecular subgroups, were obtained by in vitro enrichment. These models were characterized by an increase of NRP-1 and cancer stem cell markers (CD15, CD133 and Sox2), meanwhile a decrease of the differentiated cell marker Neurofilament-M (NF-M) was observed. Our previous work investigated potential innovative peptidomimetics that specifically target NRP-1 and showed that MR438 had a good affinity for NRP-1. This small molecule decreased the self-renewal capacity of MB stem cells for the 3 cell lines and reduced the invasive ability of DAOY and D283 stem cells while NRP-1 expression and cancer stem cell markers decreased at the same time. Possible molecular mechanisms were explored and showed that the activation of PI3K/AKT and MAPK pathways significantly decreased for DAOY cells after treatment. Finally, our results highlighted that targeting NRP-1 with MR438 could be a potential new strategy to differentiate MB stem cells and could limit medulloblastoma progression.

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Section: Discussionmentioning

confidence: 99%

Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1

et al. 2018

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“…Consistent with this, our results show that miR-148a suppresses breast cancer metastasis possibly through down-regulation of WNT1. NRP1 has recently been identified as a target gene of miR-148a in medulloblastoma [ 52 ]. In breast cancer, several studies have implicated NRP1 in various aspects of cell growth, survival, migration, and metastasis [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer

Zhang

Jasper

et al. 2016

Oncotarget

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Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis and could serve as biomarkers for diagnostic purposes. To identify miRNAs that functionally suppress metastasis of TNBC, we employed a concerted approach with selecting miRNAs that display differential expression profiles from bioinformatic analyses of breast cancer patient databases and validating top candidates with functional assays using breast cancer cell lines and mouse models. We have found that miR-148a exhibits properties as a tumor suppressor as its expression is inversely correlated with the ability of both human and mouse breast cancer cells to colonize the lung in mouse xenograft tumor models. Mechanistically, miR-148a appears to suppress the extravasation process of cancer cells, likely by targeting two genes WNT1 and NRP1 in a cell non-autonomous manner. Importantly, lower expression of miR-148a is detected in higher-grade tumor samples and correlated with increased likelihood to develop metastases and poor prognosis in subsets of breast cancer patients, particularly those with TNBC. Thus, miR-148a is functionally defined as a suppressor of breast cancer metastasis and may serve as a prognostic biomarker for this disease.

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“…In 2013, the same authors confirmed the effectiveness of miRNA-based molecular subgrouping on additional 103 MBs, including 59 formalin-fixed paraffin-embedded tissues (Kunder et al, 2013). Later on, miR-449a (Li et al, 2016) and miR-148a (Yogi et al, 2015) were reported as candidate tumor-suppressor genes and potential diagnostic markers or therapeutic targets in WNT-MBs.…”

Section: Mirna Profiling As a Tool For Mb Diagnosis And Stratificationmentioning

confidence: 90%

The Non-coding Side of Medulloblastoma

Laneve

Caffarelli

2020

Front. Cell Dev. Biol.

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Medulloblastoma (MB) is the most common pediatric brain tumor and a primary cause of cancer-related death in children. Until a few years ago, only clinical and histological features were exploited for MB pathological classification and outcome prognosis. In the past decade, the advancement of high-throughput molecular analyses that integrate genetic, epigenetic, and expression data, together with the availability of increasing wealth of patient samples, revealed the existence of four molecularly distinct MB subgroups. Their further classification into 12 subtypes not only reduced the wellcharacterized intertumoral heterogeneity, but also provided new opportunities for the design of targets for precision oncology. Moreover, the identification of tumorigenic and self-renewing subpopulations of cancer stem cells in MB has increased our knowledge of its biology. Despite these advancements, the origin of MB is still debated, and its molecular bases are poorly characterized. A major goal in the field is to identify the key genes that drive tumor growth and the mechanisms through which they are able to promote tumorigenesis. So far, only protein-coding genes acting as oncogenic drivers have been characterized in each MB subgroup. The contribution of the non-coding side of the genome, which produces a plethora of transcripts that control fundamental biological processes, as the cell choice between proliferation and differentiation, is still unappreciated. This review wants to fill this major gap by summarizing the recent findings on the impact of non-coding RNAs in MB initiation and progression. Furthermore, their potential role as specific MB biomarkers and novel therapeutic targets is also highlighted.

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MiR-148a, a microRNA upregulated in the WNT subgroup tumors, inhibits invasion and tumorigenic potential of medulloblastoma cells by targeting Neuropilin 1

Cited by 31 publications

References 45 publications

Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1

Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1

MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer

The Non-coding Side of Medulloblastoma

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