• Eukaryotic transcriptome
• biogenesis
• endogenously or exogenously
• gene regulatory pathways
• miRNAs
• prominent roles

• MicroRNAs/genetics
• Transcriptome

• Autophagy
• MAP1LC3B
• MIRI
• miR-451-3p

• Animals
• Apoptosis
• Autophagy
• Cell Line
• Down-Regulation
• Male
• MicroRNAs
• Microtubule-Associated Proteins/genetics
• Myocardial Reperfusion Injury/genetics
• Myocytes, Cardiac/metabolism
• Rats, Sprague-Dawley
• Up-Regulation
• Rats

• 2018GXNSFDA281039 Natural Science Foundation of Guangxi
• 2018GXNSFAA050110 Natural Science Foundation of Guangxi
• 2020GXNSFAA297009 Natural Science Foundation of Guangxi

• biomarker
• cancer therapy
• diagnosis
• lung cancer
• miR-451
• prognosis.

Diabetic foot ulcer (DFU) is a major concern in diabetes and its control requires in-depth molecular investigation. The present study aimed to screen the expression of microRNA-210 (miR-210) and its association in hypoxic pathway in DFU patients.

The study consists of 3 groups of circulation samples (50 in each group of: healthy volunteers, T2DM and T2DM with DFU) and 2 groups of tissue samples (10 in each group of: control and T2DM with DFU). Expression of miR-210 and hypoxia inducible factor-1 alpha (HIF-1α), and its responsive genes such as VEGF, TNF-α, IL-6, BCl2, Bax and Caspase 3 were analyzed by RT-PCR, Western blot and ELISA analyses.

The HIF-1α expression decreased in DFU patients with increased miR-210 expression in both circulation and tissue biopsies. The circulatory IL-6 and inflammatory gene TNF-α expression was increased in DFU compared to healthy controls and T2DM subjects. Further, we found there was no alteration in the angiogenic marker, VEGF expression. In comparison, anti-apoptotic BCl2 was decreased and Bax and Caspase 3 was increased in DFU tissues relative to control.

The study showed that there was an inverse relationship between miR-210 and HIF-1α expression in patients with DFU, indicating that miR-210 may regulate the expression of the hypoxic gene.

• Adult
• Apoptosis Regulatory Proteins/biosynthesis
• Apoptosis Regulatory Proteins/genetics
• Cytokines/biosynthesis
• Cytokines/genetics
• Diabetes Mellitus, Type 2/genetics
• Diabetes Mellitus, Type 2/metabolism
• Diabetic Foot/genetics
• Diabetic Foot/metabolism
• Female
• Gene Expression Regulation
• Humans
• Male
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Middle Aged
• Wound Healing

• DST-SERB
• DST-INSPIRE Program

Cancer, as one of the main causes of human deaths, is currently a significant global health challenge. Since the majority of cancer-related deaths are associated with late diagnosis, it is necessary to develop minimally invasive early detection markers to manage and reduce mortality rates. MicroRNAs (miRNAs), as highly conserved non-coding RNAs, target the specific mRNAs which are involved in regulation of various fundamental cellular processes such as cell proliferation, death, and signaling pathways. MiRNAs can also be regulated by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). They are highly stable in body fluids and have tumor-specific expression profiles, which suggest their suitability as efficient non-invasive diagnostic and prognostic tumor markers. Aberrant expression of miR-338 has been widely reported in different cancers. It regulates cell proliferation, migration, angiogenesis, and apoptosis in tumor cells.

In the present review, we have summarized all miR-338 interactions with other non-coding RNAs (ncRNAs) and associated signaling pathways to clarify the role of miR-338 during tumor progression.

It was concluded that miR-338 mainly functions as a tumor suppressor in different cancers. There were also significant associations between miR-338 and other ncRNAs in tumor cells. Moreover, miR-338 has a pivotal role during tumor progression using the regulation of WNT, MAPK, and PI3K/AKT signaling pathways. This review highlights miR-338 as a pivotal ncRNA in biology of tumor cells.

• Biomarker
• Cancer
• MiR-338
• MicroRNA
• Non-coding RNA

• AKT/mTOR
• Alergic rhinitis
• Autophagy
• PM2.5
• UBE2Q1
• miR-338–3p

• cell migration
• epithelial–mesenchymal transition
• metastasis
• miRNA
• oncomiR
• tumor invasiveness
• tumor suppressor miR

• angiogenesis
• lymphoma
• microRNA
• microenvironment
• tumor progression

• autophagy
• diabetes
• diabetic nephropathy
• microRNAs

Colorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH⁺ and CD44⁺/CD326⁺ colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients’ samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted.

• biomarker
• cancer stem cell
• colorectal cancer
• metastasis
• microRNA

• MicroRNA
• biomarker
• cancer
• exosomes
• therapeutic target

• cancer
• cancer treatment
• dysregulation
• miR-451
• target

Objective: Circular RNA is a type of endogenous RNA molecule with a stable closed-loop structure which is ubiquitous in mammals. Circular RNA HIPK3 (circHIPK3) is highly expressed in hepatocellular carcinoma and promotes the growth of hepatoma cells. However, its role in prostate cancer (PCa) has not been reported. This study aims to explore whether circHIPK3 could affect the proliferative and invasive potentials of PCa cells by regulating miRNA-338-3p.

Methods: Expression levels of circHIPK3 and miRNA-338-3p in PCa tissues and cells were determined by RT-qPCR. The regulatory effects of circHIPK3 and miRNA-338-3p on proliferative and invasive potentials of PCa cells were evaluated by CCK-8 and transwell assay, respectively. We verified the binding between miRNA-338-3p and ADAM17, as well as miRNA-338-3p and circHIPK3 through dual-luciferase reporter gene assay. Rescue experiments were conducted to clarify whether circHIPK3 affected the proliferative and invasive potentials of PCa cells by regulating miRNA-338-3p.

Results: Expression level of circHIPK3 in PCa tissues was remarkably higher than that of paracancerous tissues. Knockdown of circHIPK3 inhibited the proliferative and invasive rates of PC-3 and DU145 cells. Dual-luciferase reporter gene assay indicated that circHIPK3 could bind to miRNA-338-3p. Moreover, miRNA-338-3p expression was downregulated in PCa tissues. miRNA-338-3p expression was negatively correlated with lymph node metastasis and distant metastasis. miRNA-338-3p overexpression markedly reduced proliferative and invasive abilities of PC-3 and DU145 cells. Furthermore, ADAM17 was confirmed to be the target gene of miRNA-338-3p. Overexpression of ADAM17 enhanced proliferative and invasive abilities of PC-3 and DU145 cells. Finally, rescue experiments indicated that miRNA-338-3p knockdown in PC-3 and DU145 cells partially reversed the regulatory effects of circHIPK3 on proliferative and invasive potentials.

Conclusion: Overexpression of circHIPK3 promotes the proliferative and invasive potentials of PCa cells through sponging miRNA-338-3p to regulate ADAM17 expression, thus accelerating the malignant progression of PCa.

• ADAM17
• CircHIPK3
• miRNA-338-3p
• prostate cancer

• SW480
• colorectal cancer
• metastasis-associated in colon cancer-1
• miR-338-3p

• RUNX2
• cyclin-dependent kinase 4
• microRNA-338-3p
• mitogen-activated protein kinases pathway
• osteosarcoma

Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

• CAFs
• Cyclin D1
• GPER
• breast cancer
• c-Fos
• estrogens
• miR-338-3p

• Hepatocyte differentiation
• Micro RNA
• Tissue engineering
• Umbilical cord derived mesenchymal stem cells

• 3' Untranslated Regions
• Animals
• Cell Line, Tumor
• Cell Movement/genetics
• Genes, Tumor Suppressor
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics
• Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Stomach Neoplasms/pathology

Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs) have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral “sponge” to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

• N-cadherin
• Snail1
• epithelial-mesenchymal transition
• miR-338-3p
• sonic hedgehog

MicroRNAs (miRNAs) are involved in the epithelial-mesenchymal transition (EMT) process and are associated with metastasis in gastric cancer (GC). MiR-338-3p has been reported to be aberrantly expressed in GC. In the present study, we show that miR-338-3p inhibited the migration and invasion of GC cells in vitro. Knocking down miR-338-3p in GC cells led to mesenchymal-like changes. MiR-338-3p influenced the expression of the EMT-associated proteins by upregulating the epithelial marker E-cadherin and downregulating the mesenchymal markers, N-cadherin, fibronectin, and vimentin. In terms of mechanism, miR-338-3p directly targeted zinc finger E-box-binding protein 2 (ZEB2) and metastasis-associated in colon cancer-1 (MACC1). MiR-338-3p repressed the Met/Akt pathway after MACC1 inhibition. Reintroduction of ZEB2 and MACC1 reversed miR-338-3p-induced EMT suppression. Consistently, inverse correlations were also observed between the expression of miR-338-3p and ZEB2 or MACC1 in human GC tissue samples. In conclusion, miR-338-3p inhibited the EMT progression in GC cells by targeting ZEB2 and MACC1/Met/Akt signaling.

• MACC1
• ZEB2
• epithelial-mesenchymal transition
• gastric cancer
• miR-338-3p

• Breast cancer
• EMT
• Epithelial cell differentiation
• Epithelial-stromal interactions
• Hormonal regulation
• Signalling pathways

• Animals
• Base Sequence
• Biomarkers, Tumor/metabolism
• Carcinoma, Non-Small-Cell Lung/genetics
• Carcinoma, Non-Small-Cell Lung/pathology
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition/genetics
• Gene Knockdown Techniques
• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Mice, SCID
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Molecular Sequence Data
• Neoplasm Metastasis
• Nuclear Proteins/metabolism
• Prognosis
• Twist-Related Protein 1/metabolism
• Xenograft Model Antitumor Assays

• BT-IC
• MicroRNA
• RGD
• SLE
• UTR
• arginine-glycine-aspartine
• breast tumor initiating cell
• mRNA
• messenger RNA
• miRNA
• systemic lupus erythematosus
• untranslated terminus

• Animals
• Base Sequence
• DNA Primers
• Humans
• Integrins/physiology
• MicroRNAs/physiology

• R01 HL096887 NHLBI NIH HHS
• HL096887 NHLBI NIH HHS

AIM: To investigate the regulative effect of miRNA-338-3p (miR-338-3p) on cell growth in colorectal carcinoma (CRC).

METHODS: The lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed. The recombinant viral vector encoding the pre-miR-338-3p or miR-338-3p-inhibitor and the two packaging plasmids psPAX2 and pMD2.G were cotransfected into human embryonic kidney 293T cells to package lentivirus. The supernatant containing the lentivirus particles was harvested to determine the viral titer, and this supernatant was then used to transduce CRC-derived cell line, SW-620. Flow cytometry was utilized for sorting the green fluorescent protein (GFP)⁺ cells to establish the SW-620 cell line stably expressing pre-miR-338-3p or miR-338-3p-inhibitor. Moreover, the expression of miR-338-3p was determined by real-time reverse transcriptase polymerase chain reaction, and Western blotting was used to detect the expression of the smoothened (SMO, the possible target of miR-338-3p) protein in SW-620 cells. Furthermore, the status of CRC cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry, respectively.

RESULTS: Restriction enzyme digestion and DNA sequencing demonstrated that the lentiviral vector pLV-THM-miR-338-3p and pLV-THM-miR-338-3p-inhibitor were constructed successfully. GFP was expressed after the SW-620 cells were transduced by the lentivirus. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p was significantly increased (relative expression 3.91 ± 0.51 vs 2.36 ± 0.44, P < 0.01). Furthermore, overexpression of miR-338-3p inhibited the expression of SMO protein in SW-620 cells, which showed obviously suppressed proliferation ability [cellular proliferation inhibition rate (CPIR) 61.9% ± 5.2% vs 41.6% ± 4.8%, P < 0.01]. Expression of miR-338-3p in SW-620 cells transduced with the lentivirus pLV-THM-miR-338-3p-inhibitor was significantly decreased (relative expression 0.92 ± 0.29 vs 2.36 ± 0.44, P < 0.01). Moreover, the downregulated expression of miR-338-3p caused upregulated expression of the SMO protein in SW-620 cells, which showed significantly enhanced proliferation ability (CPIR 19.2% ± 3.8% vs 41.6% ± 4.8%, P < 0.01). However, anti-SMO-siRNA largely, but not completely, reversed the effects induced by blockage of miR-338-3p, suggesting that the regulative effect of miR-338-3p on CRC cell growth was indeed mediated by SMO.

CONCLUSION: miR-338-3p could suppress CRC growth by inhibiting SMO protein expression.

• Colorectal carcinoma
• Hsa-miRNA-338-3p
• Smoothened
• Lentivirus

• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Genetic Vectors
• HEK293 Cells
• Humans
• Lentivirus/genetics
• MicroRNAs/metabolism
• RNA Interference
• Receptors, G-Protein-Coupled/genetics
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• Smoothened Receptor
• Transduction, Genetic
• Transfection
• Up-Regulation

• dynamic expression
• erythrogenesis
• human embryonic stem cells
• mirnas

• Cell Differentiation/genetics
• Embryonic Stem Cells/cytology
• Embryonic Stem Cells/physiology
• Erythroid Cells/cytology
• Erythroid Precursor Cells/cytology
• Erythroid Precursor Cells/physiology
• Flow Cytometry
• Humans
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Microarray Analysis

MicroRNAs, a new class of key regulators of gene expression, have been shown to be involved in diverse biological processes and linked to many human diseases. To elucidate miRNA function from a global perspective, we constructed a conserved miRNA co-expression network by integrating multiple human and mouse miRNA expression data. We found that these conserved co-expressed miRNA pairs tend to reside in close genomic proximity, belong to common families, share common transcription factors, and regulate common biological processes by targeting common components of those processes based on miRNA targets and miRNA knockout/transfection expression data, suggesting their strong functional associations. We also identified several co-expressed miRNA sub-networks. Our analysis reveals that many miRNAs in the same sub-network are associated with the same diseases. By mapping known disease miRNAs to the network, we identified three cancer-related miRNA sub-networks. Functional analyses based on targets and miRNA knockout/transfection data consistently show that these sub-networks are significantly involved in cancer-related biological processes, such as apoptosis and cell cycle. Our results imply that multiple co-expressed miRNAs can cooperatively regulate a given biological process by targeting common components of that process, and the pathogenesis of disease may be associated with the abnormality of multiple functionally cooperative miRNAs rather than individual miRNAs. In addition, many of these co-expression relationships provide strong evidence for the involvement of new miRNAs in important biological processes, such as apoptosis, differentiation and cell cycle, indicating their potential disease links.

• Animals
• Base Sequence
• Cluster Analysis
• Conserved Sequence
• Gene Expression Profiling/methods
• Gene Expression Regulation
• Genetic Techniques
• Genomics
• Humans
• Mice
• MicroRNAs/metabolism
• Models, Genetic
• Models, Statistical
• Molecular Sequence Data
• Probability
• Protein Biosynthesis
• Signal Transduction

AIM: To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.

METHODS: The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%).

RESULTS: Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups.

CONCLUSION: This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact.

• MicroRNA
• Prognosis
• Recurrence
• Gastric cancer