Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Role of Mir-148a in Cancer.

ABSTRACT: MicroRNAs (miRNAs) are highly conserved noncoding RNAs of about 19-25 nucleotides. Through specifically pairing with complementary sites in 3' untranslated regions (UTRs) of target mRNAs, they mediate post-transcriptional silencing. MicroRNAs have been implicated in many physiological processes including proliferation, differentiation, development, apoptosis, and metabolism. In recent years many studies have revealed that the aberrant expression of miRNA is closely related to oncogenesis and is now an intense field of study. Mir-148a is aberrantly expressed in various cancers and has been identified as an oncogenic or tumor suppressor with crucial roles in the molecular mechanisms of oncogenesis. In this review, we have summarized the role of mir-148a in the oncogenic pathways of gastric, liver, breast and urogenital cancers, and in neurogliocytoma oncogenesis. Studying the functional role of mir-148a is crucial in discovering novel tumor molecular markers and identifying potential therapeutic targets.

SUBMITTER: Li Y

PROVIDER: S-EPMC4934031 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The Role of Mir-148a in Cancer.

Li Yue Y Deng Xiyun X Zeng Xiaomin X Peng Xiaoning X

Journal of Cancer 20160621 10

MicroRNAs (miRNAs) are highly conserved noncoding RNAs of about 19-25 nucleotides. Through specifically pairing with complementary sites in 3' untranslated regions (UTRs) of target mRNAs, they mediate post-transcriptional silencing. MicroRNAs have been implicated in many physiological processes including proliferation, differentiation, development, apoptosis, and metabolism. In recent years many studies have revealed that the aberrant expression of miRNA is closely related to oncogenesis and is ...[more]

PMID: 27390598

Similar Datasets

Role of miR-148a in hepatitis B associated hepatocellular carcinoma.

Project description:Hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. HBx transcriptionally up-regulates the expression of a unique gene, URG11, which in turn transcriptionally up-regulates ?-catenin, thereby contributing importantly to hepatocarcinogenesis. HBx and URG11 also alter the expression of multiple microRNAs, and by miRNA array analysis, both were shown to promote the expression of miR-148a. Elevated miR-148a was also seen in HBx positive liver samples from infected patients. To study the function of miR-148a, anti-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation, cell cycle progression, cell migration, anchorage independent growth in soft agar and subcutaneous tumor formation in SCID mice. Introduction of anti-miR-148a increased PTEN protein and mRNA expression, suggesting that PTEN was targeted by miR-148a. Anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants in the 3'UTR of PTEN mRNA. Introduction of anti-miR-148a also resulted in depressed Akt signaling by HBx and URG11, resulting in decreased expression of ?-catenin. Thus, miR-148a may play a central role in HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type.

| S-EPMC3322146 | biostudies-literature

Quantitative Proteomics of miR-148a in gastric cancer cells

Project description:A quantitative proteomics combined with stable isotope labeling was applied to identify the global profile of miR-148a-regulated downstream proteins in AGS cancer cells. For proteomic analysis, cells were treated with miR-148a mimic (Pre-miR-148a) or miR-148a negative control (miR-CTL) and the downstream protein expression level (Pre-miR-148a/miR-CTL) were quantified using iTRAQ approach. Bioinformatics pipeline: The peak list in the resultant MS/MS spectra were generated by Mascot Distiller v2.1.1.0 and searched using Mascot v2.2 against the International Protein Index (IPI) human database (v. 3.64, 84032 sequences). The Mascot search parameters were +-0.1 Da for MS tolerance, +-0.1 Da for MS/MS mass tolerance, allowances for two missed cleavages, and variable modifications of deamidation (NQ), oxidation (M), iTRAQ (N terminal), iTRAQ (K), and MMTS (C). Protein quantitation were calculated using the Multi-Q software v1.6.5.4 with a dynamic range filter of ion count > 30.

2013-07-24 | PXD000190 | Pride

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11.

Project description:Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (p < 0.05). Overexpression of miR-148a selectively inhibited CRC cell viability (p < 0.001), while weakly affecting normal CCD 841 CoN cell survival (p < 0.05). At the cellular level, miR-148a-3p mimics promoted apoptotic cell death via caspase-3 activation (p < 0.001), accumulation of mitochondrial reactive oxygen species (ROS) (p < 0.001), and membrane depolarization (p < 0.001). Moreover, miR-148a-3p overexpression induced lipid peroxidation (p < 0.01), GPX4 downregulation (p < 0.01), and ferroptosis (p < 0.01), as revealed by intracellular and mitochondrial iron accumulation and ACSL4/TFRC/Ferritin modulation. In addition, levels of SLC7A11 mRNA and protein, the cellular targets of miR-148a-3p predicted by bioinformatic tools, were suppressed by miR-148a-3p's overexpression. On the contrary, the downregulation of miR-148a-3p boosted SLC7A11 gene expression and suppressed ferroptosis. Together, these in vitro findings reveal that miR-148a-3p can function as a tumor suppressor in CRC by targeting SLC7A11 and activating ferroptosis, opening new perspectives for the rationale of therapeutic strategies through targeting the miR-148a-3p/SLC7A11 pathway.

| S-EPMC10486764 | biostudies-literature

From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia.

Project description:Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1? and NF-?Bp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

| S-EPMC7239341 | biostudies-literature

Stable duplex-linked antisense targeting miR-148a inhibits breast cancer cell proliferation.

Project description:MicroRNAs (miRNAs) regulate cancer cell proliferation by binding directly to the untranslated regions of messenger RNA (mRNA). MicroRNA-148a (miR-148a) is expressed at low levels in breast cancer (BC). However, little attention has been paid to the sequestration of miR-148a. Here, we performed a knockdown of miR-148a using anti-miRNA oligonucleotides (AMOs) and investigated the effect on BC cell proliferation. BC cell proliferation was significantly suppressed by AMO flanked by interstrand cross-linked duplexes (CL-AMO), whereas single-stranded and commercially available AMOs had no effect. The suppression was caused by sequestering specifically miR-148a. Indeed, miR-148b, another member of the miR-148 family, was not affected. Importantly, the downregulation of miR-148a induced a greater and longer-lasting inhibition of BC cell proliferation than the targeting of oncogenic microRNA-21 (miR-21) did. We identified thioredoxin-interacting protein (TXNIP), a tumor suppressor gene, as a target of miR-148a and showed that CL-AMO provoked an increase in TXNIP mRNA expression. This study provide evidence that lowly expressed miRNAs such as miR-148a have an oncogenic function and might be a promising target for cancer treatment.

| S-EPMC8169724 | biostudies-literature

Hypoxia-Induced miR-148a Downregulation Contributes to Poor Survival in Colorectal Cancer.

Project description:Hypoxia is an extensively investigated condition due to its contribution to various pathophysiological processes including cancer progression and metastasis formation. MicroRNAs (miRNAs) are well-known post-transcriptional gene expression regulators. However, their contribution to molecular response to hypoxia is highly dependent on cell/tissue types and causes of hypoxia. One of the most important examples is colorectal cancer, where no consensus on hypoxia-regulated miRNAs has been reached so far. In this work, we applied integrated mRNA and small RNA sequencing, followed by bioinformatics analysis, to study the landscape of hypoxia-induced miRNA and mRNA expression alterations in human colorectal cancer cell lines (HT-29 and Caco-2). A hypoxic microenvironment was chemically modeled using two different treatments: cobalt(II) chloride and oxyquinoline. Only one miRNA, hsa-miR-210-3p, was upregulated in all experimental conditions, while there were nine differentially expressed miRNAs under both treatments within the same cell line. Further bioinformatics analysis revealed a complex hypoxia-induced regulatory network: hypoxic downregulation of hsa-miR-148a-3p led to the upregulation of its two target genes, ITGA5 and PRNP, which was shown to be a factor contributing to tumor progression and poor survival in colorectal cancer patients.

| S-EPMC8202010 | biostudies-literature

miR-148a-mediated estrogen-induced cholestasis in intrahepatic cholestasis of pregnancy: Role of PXR/MRP3.

Project description:Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic liver disease while the biochemical characteristic is the elevated level of total bile acid (TBA). The present study investigated whether miR-148a mediates the induced effect of estrogen on the development of ICP and the proper mechanism: PXR/MRP3 signal pathway. mRNA expression was detected by qPCR, protein expression was detected by western blotting, the concentration of estrogen and TBA were detected by reagent kit respectively. In the cinical research, it was found that miR-148a expression was positive related with the concentration of TBA in the serum of ICP patients. In in vitro research, estradiol (500 nmol/L, 12 h) significantly upregulated miR-148a expression and LV-148a-siRNA inhibited the function of estradiol (500 nmol/L, 48 h) on TBA secretion. In addition, gene silence of miR-148a upregulated PXR expression which was inhibited by estradiol in LO2 cells. Pretreatment of rifampin (10 ?mol/L), the agonist of PXR alleviated the TBA secretion induced by estradiol (500 nmol/L, 48 h). miR-148a-siRNA and PXR had a synergistic action on TBA secretion of LO2. Both of miR-148a-siRNA and rifampin (10 ?mol/L) inhibited the upregulated effect of estradiol on MRP3 expression. This research has demonstrated that miR-148a may be involved in the induction of estrogen on ICP via PXR signal pathway, and MRP3 may be involved.

| S-EPMC5457162 | biostudies-literature

The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.

Project description:MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.

| S-EPMC3561221 | biostudies-literature

miR-148a suppresses inflammation in lipopolysaccharide-induced endometritis.

Project description:Endometritis is a postnatal reproductive disorder disease, which leads to great economic losses for the modern dairy industry. Emerging evidence indicates that microRNAs (miRNAs) play a pivotal role in a variety of diseases and have been identified as critical regulators of the innate immune response. Recent miRNome profile analysis revealed an altered expression level of miR-148a in cows with endometritis. Therefore, the present study aims to investigate the regulatory role of miR-148a in the innate immune response involved in endometritis and estimate its potential therapeutic value. Here, we found that miR-148a expression in lipopolysaccharide (LPS)-stimulated endometrial epithelial cells was significantly decreased. Our results also showed that overexpression of miR-148a using agomiR markedly reduced the production of pro-inflammatory cytokines, such as IL-1β and TNF-α. Moreover, overexpression of miR-148a also suppressed NF-κB p65 activation by targeting the TLR4-mediated pathway. Subsequently, we further verified that miR-148a repressed TLR4 expression by binding to the 3'-UTR of TLR4 mRNA. Additionally, an experimental mouse endometritis model was employed to evaluate the therapeutic value of miR-148a. In vivo studies suggested that up-regulation of miR-148a alleviated the inflammatory conditions in the uterus as evidenced by H&E staining, qPCR and Western blot assays, while inhibition of miR-148a had inverse effects. Collectively, pharmacologic stabilization of miR-148a represents a novel therapy for endometritis and other inflammation-related diseases.

| S-EPMC6933404 | biostudies-literature

Human Papillomavirus 16 Oncoproteins Downregulate the Expression of miR-148a-3p, miR-190a-5p, and miR-199b-5p in Cervical Cancer.

Project description:Almost all cervical cancers are associated with human papillomavirus (HPV); however, the majority of women infected with this virus do not develop cervical cancer. Therefore, new markers are needed for reliable screening of cervical cancer, especially in relation to HPV infection. We aimed to identify potential microRNAs that may serve as diagnostic markers for cervical cancer development in high-risk HPV-positive patients. We evaluated the microRNA expression profiles in 12 cervical tissues using the hybridization method and verified them by quantitative polymerase chain reaction (qPCR). Finally, we evaluated the effects of HPV16 oncoproteins on the expression of selected microRNAs using cervical cancer cells (CaSki and SiHa) and RNA interference. With the hybridization method, eight microRNAs (miR-9-5p, miR-136-5p, miR-148a-3p, miR-190a-5p, miR-199b-5p, miR-382-5p, miR-597-5p, and miR-655-3p) were found to be expressed differently in the HPV16-positive cervical cancer group and HPV16-positive normal group (fold change ? 2). The results of qPCR showed that miR-148a-3p, miR-190a-5p, miR-199b-5p, and miR-655-3p levels significantly decreased in the cancer group compared with the normal group. Upon silencing of HPV16 E5 and E6/E7, miR-148a-3p levels increased in both cell lines. Silencing of E6/E7 in SiHa cells led to the increase in miR-199b-5p and miR-190a-5p levels. Three HPV16 oncoproteins (E5, E6, and E7) downregulate miR-148a-3p, while E6/E7 inhibit miR-199b-5p and miR-190a-5p expression in cervical carcinoma. The three microRNAs, miR-148a-3p, miR-199b-5p, and miR-190a-5p, may be novel diagnostic biomarkers for cervical cancer development in high-risk HPV-positive patients.

| S-EPMC6304571 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data