Role of lncRNAs in the Development of an Aggressive Phenotype in Gallbladder Cancer

Long non-coding RNAs are sequences longer than 200 nucleotides that are involved in different normal and abnormal biological processes exerting their effect on proliferation and differentiation, among other cell features. Functionally, lncRNAs can regulate gene expression within the cells by acting at transcriptional, post-transcriptional, translational, or post-translational levels. However, in pathological conditions such as cancer, the expression of these molecules is deregulated, becoming elements that can help in the acquisition of tumoral characteristics in the cells that trigger carcinogenesis and cancer progression. Specifically, in gallbladder cancer (GBC), recent publications have shown that lncRNAs participate in the acquisition of an aggressive phenotype in cancer cells, allowing them to acquire increased malignant capacities such as chemotherapy resistance or metastasis, inducing a worse survival in these patients. Furthermore, lncRNAs are useful as prognostic and diagnostic biomarkers since they have been shown to be differentially expressed in tumor tissues and serum of individuals with GBC. Therefore, this review will address different lncRNAs that could be promoting malignant phenotypic characteristics in GBC cells and lncRNAs that may be useful as markers due to their capability to predict a poor prognosis in GBC patients.

Download Full-text

miR-8b is involved in brain and eye regeneration of Dugesia japonica in head regeneration

Biology Open ◽

10.1242/bio.058538 ◽

2021 ◽

Vol 10 (6) ◽

Author(s):

Hongjin Liu ◽

Qian Song ◽

Hui Zhen ◽

Hongkuan Deng ◽

Bosheng Zhao ◽

...

Keyword(s):

Regulate Gene Expression ◽

Planarian Regeneration ◽

Evolutionarily Conserved ◽

Proliferation And Differentiation ◽

Important Regulator ◽

Dugesia Japonica ◽

Non Coding Rnas ◽

Available Information ◽

Head Regeneration

ABSTRACT MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that regulate gene expression at the translation level in cell growth, proliferation and differentiation. In addition, some types of miRNAs have been proven to be key modulators of both CNS development and plasticity, such as let-7, miR-9 and miR-124. In this research, we found miR-8b acts as an important regulator involved in brain and eyespot regeneration in Dugesia japonica. miR-8b was highly conserved among species and was abundantly expressed in central nervous system. Here, we detected the expression dynamics of miR-8b by qPCR during the head regeneration of D. japonica. Knockdown miR-8b by anti-MIRs method caused severe defects of eyes and CNS. Our study revealed the evolutionary conserved role of miR-8b in the planarian regeneration process, and further provided more research ideas and available information for planarian miRNAs.

Download Full-text

miR-205 in Breast Cancer: State of the Art

International Journal of Molecular Sciences ◽

10.3390/ijms22010027 ◽

2020 ◽

Vol 22 (1) ◽

pp. 27

Author(s):

Ilaria Plantamura ◽

Alessandra Cataldo ◽

Giulia Cosentino ◽

Marilena V. Iorio

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Normal Breast ◽

Response To Therapy ◽

Aberrant Expression ◽

Open Questions ◽

Tumor Tissues ◽

Breast Physiology ◽

Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

Download Full-text

Dysregulation of miRNA in cancer progression

10.31219/osf.io/u429y ◽

2021 ◽

Author(s):

Rucha P.

Keyword(s):

Gene Regulation ◽

Cancer Progression ◽

Therapeutic Target ◽

Chromosomal Abnormalities ◽

Human Cancer ◽

Epigenetic Modification ◽

Therapeutic Applications ◽

Non Coding Rnas ◽

Transcriptional Gene Regulation

MicroRNAs (miRNAs) are a category of highly conserved tiny non-coding RNAs that play a role in post-transcriptional gene regulation. Numerous studies have shown the role of dysregulated miRNA in a variety of illnesses, including human cancer. MiRNA is dysregulated by a variety of processes, including dysregulation of miRNA synthesis, aberrant miRNA transcription, dysregulated epigenetic modification, and chromosomal abnormalities. MiRNAs that are overexpressed have been shown to influence cancer's hallmarks. Recent research has shown miRNA's potential as a therapeutic target and biomarker. In this review, we discussed the synthesis and regulation of miRNA, as well as its dysregulation in human cancer and other disorders, as well as some of the therapeutic applications of miRNA.

Download Full-text

Long non-coding RNA MEG3 silencing and microRNA-214 restoration elevate osteoprotegerin expression to ameliorate osteoporosis by limiting TXNIP

10.21203/rs.2.19130/v1 ◽

2019 ◽

Author(s):

Rui Ding ◽

ZhengTao Gu ◽

ChangSheng Yang ◽

CaiQiang Huang ◽

QingChu Li ◽

...

Keyword(s):

Interacting Protein ◽

Blood Samples ◽

Rat Models ◽

Thioredoxin Interacting Protein ◽

Non Coding Rna ◽

Proliferation And Differentiation ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Rat Osteoblasts

Abstract BackgroundLong non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA MEG3 in osteoporosis (OP) has rarely been discussed. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA-214 (miR-214) and thioredoxin-interacting protein (TXNIP)MethodsRat models of OP were established. MEG3, miR-214, and TXNIP mRNA expression in rat femoral tissues was detected, along with TXNIP, PCNA, cyclin D1, OCN, RUNX2, Osteolix, OPG, and PANKL protein expression. Ca, P and ALP contents in rat blood samples were also determined. Primary osteoblasts were isolated and cultured. Viability, COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected.ResultsMEG3 and TXNIP were overexpressed while miR-214 was underexpressed in femoral tissues of OP rats. MEG3 silencing and miR-214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, the number of osteoblasts, collagen area and OPG expression, and downregulated PANKL of femoral tissues in OP rats. MEG3 silencing and miR-214 overexpression elevated Ca and P contents and reduced ALP content in OP rats’ blood, elevated viability, differentiation ability, COL-I and COL-Χ contents and ALP activity, and abated COL-II content of osteoblasts. MEG3 specifically bound to miR-214 to regulate TXNIP.ConclusionCollectively, we demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating TXNIP, which further improves OP.

Download Full-text

The Osteoporosis/Microbiota Linkage: The Role of miRNA

International Journal of Molecular Sciences ◽

10.3390/ijms21238887 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8887 ◽

Cited By ~ 1

Author(s):

Massimo De Martinis ◽

Lia Ginaldi ◽

Alessandro Allegra ◽

Maria Maddalena Sirufo ◽

Giovanni Pioggia ◽

...

Keyword(s):

Dynamic Equilibrium ◽

Treatment Strategies ◽

Therapeutic Agents ◽

Osteoporosis Prevention ◽

Regulate Gene Expression ◽

Molecular Biotechnology ◽

Non Coding Rnas ◽

The Relationship ◽

Complementary Mechanism

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

Download Full-text

The Role of miR-210 in the Biological System: A Current Overview

Human Heredity ◽

10.1159/000509280 ◽

2019 ◽

Vol 84 (6) ◽

pp. 233-239

Author(s):

Xu Hui ◽

Hisham Al-Ward ◽

Fahmi Shaher ◽

Chun-Yang Liu ◽

Ning Liu

Keyword(s):

Gene Expression ◽

Regulation Of Gene Expression ◽

Low Oxygen ◽

Cellular Functions ◽

Regulate Gene Expression ◽

System A ◽

Non Coding Rnas ◽

Post Transcriptional Regulation ◽

A Current

Background: MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. Summary: miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. Key Message: miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

Download Full-text

MiR-147: Functions and Implications in Inflammation and Diseases

MicroRNA ◽

10.2174/2211536610666210707113605 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ling Lin ◽

Kebin Hu

Keyword(s):

Gene Expression ◽

Infectious Disease ◽

Neurodegenerative Disorder ◽

Mrna Translation ◽

Transcriptional Level ◽

Regulate Gene Expression ◽

Inflammatory Bowel ◽

Non Coding Rnas ◽

Regulate Gene

: MicroRNAs (miRNAs) are small non-coding RNAs (19~25 nucleotides) that regulate gene expression at a post-transcriptional level through repression of mRNA translation or mRNA decay. miR-147, which was initially discovered in mouse spleen and macrophages, has been shown to correlate with coronary atherogenesis and inflammatory bowel disease and modulate macrophage functions and inflammation through TLR-4. The altered miR-147 level has been shown in various human diseases, including infectious disease, cancer, cardiovascular disease, a neurodegenerative disorder, etc. This review will focus on the current understanding regarding the role of miR-147 in inflammation and diseases.

Download Full-text

jouvence, a new human H/ACA snoRNA involves in the control of cell proliferation and differentiation

10.1101/2020.06.17.157321 ◽

2020 ◽

Author(s):

Flaria El-Khoury ◽

Jérôme Bignon ◽

Jean-René Martin

Keyword(s):

Cell Proliferation ◽

Small Nucleolar Rnas ◽

Primary Cells ◽

Cell Proliferation And Differentiation ◽

Cancerous Cell ◽

Proliferation And Differentiation ◽

Non Coding Rnas ◽

Nucleolar Rnas

AbstractSmall nucleolar RNAs (snoRNAs) are non-coding RNAs conserved from archeobacteria to mammals. In humans, various snoRNAs have been associated with pathologies as well as with cancer. Recently in Drosophila, a new snoRNA named jouvence has been involved in lifespan. Since snoRNAs are well conserved through evolution, both structurally and functionally, jouvence orthologue has been identified in human, allowing hypothesizing that jouvence could display a similar function (increasing healthy lifespan) in human. Here, we report the characterization of the human snoRNA-jouvence, which was not yet annotated in the genome. We show, both in stably cancerous cell lines and in primary cells, that its overexpression stimulates the cell proliferation. In contrast, its knockdown, by siRNA leads to an opposite phenotype, a decrease in cell proliferation. Transcriptomic analysis reveals that overexpression of jouvence leads to a dedifferentiation signature of the cells, a cellular effect comparable to rejuvenation. Inversely, the knockdown of jouvence leads to a decrease of genes involved in ribosomes biogenesis and spliceosome in agreement with the canonical role of a H/ACA box snoRNA. In this context, jouvence could represent a now tool to fight against the deleterious effect of aging, as well as a new target in cancer therapy.

Download Full-text

Cancer associated-fibroblast-derived exosomes in cancer progression

Molecular Cancer ◽

10.1186/s12943-021-01463-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Chao Li ◽

Adilson Fonseca Teixeira ◽

Hong-Jian Zhu ◽

Peter ten Dijke

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Chemotherapy Resistance ◽

Cell Types ◽

Cancer Therapies ◽

Cancer Associated Fibroblast

AbstractTo identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.

Download Full-text

The role of HOMER3 in liver cancer progression.

Journal of Global Oncology ◽

10.1200/jgo.2019.5.suppl.89 ◽

2019 ◽

Vol 5 (suppl) ◽

pp. 89-89

Author(s):

Precious Takondwa Makondi

Keyword(s):

Liver Cancer ◽

Viral Hepatitis ◽

Cancer Progression ◽

Alcohol Intake ◽

Clinical Stage ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Obesity And Diabetes ◽

Tumor Tissues

89 Background: Liver cancer (LC) is in the seventh most common cancer and the fourth largest cause of cancer deaths. Although significant progress has been made in the prevention and treatment of viral hepatitis; alcoholic liver disease, obesity and diabetes are now emerging as major causes for LC. Recently there has been increase in identification of biomarkers which can predict LC risk and disease progression, but the roles of HOMER3 gene in LC are not known. Methods: First the expression of HOMER3 between normal and tumor tissues was determined using The Cancer Genome Atlas (TCGA), Genetic Expression Omnibus (GEO) and protein atlas datasets. HOMER3 expression at different clinical stage and overall survival (OS) was also determined. The role of HOMER3 on OS in relation to cancer stage, hepatitis virus infection and alcohol intake was also determined. STRING database determined HOMER3 interaction network and TCGA was used to verify the correlation status, and the roles of the network genes on OS. The pathways enriched by HOMER3 were determined by Gene Set Enrichment Analysis (GSEA). Results: HOMER3 was significantly highly expressed in tumor tissues as compared to normal tissues. The expression of HOMER3 correlated positively with clinical stage, with highest expression in advanced stages (Stage 3 and 4), and high HOMER3 expression was associated with poor OS. HOMER3’ s high expression was associated with poor OS in advanced stage, alcohol intake, and in those negative of viral hepatitis infection. HOMER3 interacted with HOMER1, SHANK1, GRM5, GRM1, DLGAP1, SHANK2, DLG4, SHANK3, DLG2 and DLGAP4, with positive correlation to HOMER1, SHANK1, GRM5, GRM1, DLGAP1, DLG4 and DLGAP4 and negative correlation to SHANK2, SHANK3 and DLG2. HOMER1 and DLGAP4 high expression were associated with poor OS while SHANK2, SHANK3 and DLG2 high expression were associated with favorable OS. GRM5 and GRM1 high expression were associated with favorable OS despite being positively correlated with HOMER3. ECM receptor interaction and Notch signaling were the upregulated pathways while Metabolism of xenobiotics by cytochrome p450 and PPAR signaling were the downregulated pathways. Conclusions: HOMER3 may is have a role in liver cancer progression of which its targeting may improve LC outcome.

Download Full-text