The role of the miR‐148/‐152 family in physiology and disease

Friedrich, Michael W.; Pracht, Katharina; Mashreghi, Mir‐Farzin; Jäck, Hans‐Martin; Radbruch, Andreas; Seliger, Barbara

doi:10.1002/eji.201747132

Cited by 96 publications

(75 citation statements)

References 134 publications

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“…Consistent with our finding, tumor suppressive functions of miR-148a-3p have been demonstrated in many cancer types (35,37), including colorectal cancer (36,41). Indeed, miR-148a-3p has been reported to be downregulated in tumors, compared with their normal counterpart, which often correlated with advanced stage, where miR-148a-3p silencing was caused by DNA hypermethylation of its promotor (35,37,42). Decreased levels of miR-148a-3p were associated with poor clinical outcomes in a variety of cancers (43)(44)(45).…”

Section: Discussionsupporting

confidence: 93%

“…Recent reports have suggested that miR-148a-3p can work as a tumor suppressive miRNA that is frequently downregulated in colorectal cancer and other malignancies (35)(36)(37). To confirm the tumor suppressive function of miR-148a-3p in vitro, we used exogenous overexpression by transfecting miR-148a-3p mimic using a colorectal cancer cell line, HCT116 (Fig.…”

Section: Mir-148a-3p As a Tumor Suppressor In Colorectal Cancermentioning

confidence: 99%

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miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Ashizawa

Okayama

Ishigame

et al. 2019

Molecular Cancer Research

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Immunotherapy against the interaction between programmed cell death 1/programmed cell death ligand 1 (PD-L1) has emerged as a promising strategy for colorectal cancer with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). The study aimed to identify miRNAs that posttranscriptionally control PD-L1 expression on tumor cells and also regulate immune evasion. A comprehensive miRNA screening using The Cancer Genome Atlas (TCGA) dataset (n ¼ 260) combined with eight different miRNA target prediction programs resulted in the identification of a tumor suppressive miRNA, miR-148a-3p, as a potential negative regulator of PD-L1 expression, particularly in dMMR/MSI-H colorectal cancer. Using multiple cohorts of colorectal cancer, including TCGA data, a microarray dataset (n ¼ 148), and formalin-fixed, paraffin-embedded samples (n ¼ 395), we found that the expression of miR-148a-3p was decreased in dMMR/MSI-H tumors, correlating inversely with PD-L1 levels. We demonstrate that miR-148a-3p directly binds to the 3 0 -untranslated region of PD-L1, thereby reducing whole-cell and cell surface PD-L1 levels in HCT116 and SW837 cell lines. Overexpression of miR-148a-3p repressed IFNg-induced PD-L1 expression on tumor cells and consequently diminished T-cell apoptosis in a coculture model of IL2-activated T cells and IFNg-treated tumor cells. In conclusion, our data support a regulatory mechanism of PD-L1 expression on tumor cells and immune suppression via miR-148a-3p downregulation in colorectal cancer. Implications:This study provides novel evidence that miR-148a-3p negatively regulates tumor cell PD-L1 expression and decreased levels of miR-148a-3p contributes to the immunosuppressive tumor microenvironment.

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Section: Discussionsupporting

confidence: 93%

Section: Mir-148a-3p As a Tumor Suppressor In Colorectal Cancermentioning

confidence: 99%

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Ashizawa

Okayama

Ishigame

et al. 2019

Molecular Cancer Research

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“…Again, miR‐148a is the most expressed milk microRNA, and it is consistently reported in all milk small RNA sequencing, supporting its evolutionary importance in lactation and possibly for the newborn's development and health (Friedrich et al., ; Zempleni et al., ). Moreover, the sequences of human and bovine miR‐148a are identical.…”

Section: Micrornas Found In Milk From Other Speciesmentioning

confidence: 81%

Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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MicroRNAs are small noncoding RNAs responsible for regulating 40% to 60% of gene expression at the posttranscriptional level. The discovery of circulating microRNAs in several biological fluids opened the path for their study as biomarkers and long‐range cell‐to‐cell communication mediators. Their transfer between individuals in the case of blood transfusion, for example, and their high enrichment in milk have sparked the interest for microRNA transfer through diet, especially from mothers to infants during breastfeeding. The extension of such paradigm led to the study of milk microRNAs in the case of cow or goat milk consumption in adults. Here we provide a comprehensive critical review of the key findings surrounding milk microRNAs in human, cow, and goat milk among other species. We discuss the data on their biological properties, their use as disease biomarkers, their transfer between individuals or species, and their putative or verified functions in health and disease of infants and adult consumers. This work is based on all the literature available and integrates all the results, theories, debates, and validation studies available so far on milk microRNAs and related areas of investigations. We critically discuss the limitations and outline future aspects and avenues to explore in this rapidly growing field of research that could impact public health through infant milk formulations or new therapies. We hope that this comprehensive review of the literature will provide insight for all teams investigating milk RNAs’ biological activities and help ensure the quality of future reports.

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“…In the human genome, the miR-148-family consists of 3 members that are located in different chromosomal regions: miR-148a is at 7p15.2, miR-148b is at 12q13.13 and miR-152 is at 17q21.32. 27,28 The mature sequences of the guide strands of these miRNAs are similar and the seed sequences (UCAGUGCA) are identical. 29 Most analyses have focused on guide strands of the miR-148-family in normal physiological conditions or in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

et al. 2018

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We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre‐miR‐148a (miR‐148a‐5p: the passenger strand and miR‐148a‐3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR‐148a‐5p and miR‐148a‐3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre‐miR‐148a had tumor‐suppressive roles in PDAC cells. In silico database and genome‐wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR‐148a‐5p targets (PHLDA2,LPCAT2 and AP1S3) and miR‐148a‐3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre‐miR‐148a (miR‐148‐5p) is a new concept in cancer research. Novel approaches that identify tumor‐suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.

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The role of the miR‐148/‐152 family in physiology and disease

Cited by 96 publications

References 134 publications

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

miRNA-148a-3p Regulates Immunosuppression in DNA Mismatch Repair–Deficient Colorectal Cancer by Targeting PD-L1

Milk MicroRNAs in Health and Disease

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

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