Research Highlights: The Role of Small RNAs in the Production of Blood Cells

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Original Article:

  • Hematopoiesis is the process by which the body produces blood cells and blood plasma.
  • Blood cells are divided into three lineages: erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages).
  • Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs).
  • miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells.
  • MicroRNAs are transcribed by RNA polymerases II and III, generating precursors that undergo a series of cleavage events to form mature microRNA.
  • Evidence shows that miRNAs play an important role in haematopoiesis.
  • Myeloid and erythroid differentiation is blocked by the overexpression of miR-15a.
  • miR-221, miR-222, and miR-24 inhibit the erythropoiesis.
  • miR-150 plays a role in B and T cell differentiation.
  • miR-146 and miR-10a are downregulated in megakaryopoiesis.
  • Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas.
  • In this review, we have focused on discussing the role of miRNA in haematopoiesis.


ANNALS EXPRESS: Discovery of microRNA expression profiles involved in regulating TGF-β2 expression in the tears of dry eye patients

Background: To date, the difference in microRNA (miR) expression profiles in tears of dry eye patients and healthy people has not been reported. In current study, we evaluated the significance of miRs and transforming growth factor beta2 (TGF-β2) in distinguishing dry eye.

Methods: 138 patients with dry eye from October 2017 to October 2018 were selected. During the same period, 138 healthy persons were collected. All patients were followed up for 12 months through outpatient, telephone or medical records, and the time of corneal injury was recorded.

Results: Compared with healthy people, TGF-β2 levels in dry eye patients were significantly decreased (P<0.05). Array analysis, predictive software, and dual-luciferase reporter assays showed that miR-450b-5p, miR-1283, and miR-3671 can target TGF-β2 expression. Tear miR-450b-5p, miR-1283, and miR-3671 levels were significantly higher in dry eye patients than healthy people. A logistic regression model combining miR-450b-5p, miR-1283, miR-3671, and TGF-β2 was performed. This model presented a high discriminating value (AUC: 0.907, 0.876-0.939, P<0.001) than any single indicator, and the sensitivity and specificity were 77.7% and 92.7%, respectively. Compared with the low miR-450b-5p, low miR-1283, low miR-3671 and high TGF-β2 groups, the high miR-450b-5p, high miR-1283, high miR-3671 and low TGF-β2 groups had a significantly higher probability of corneal injury (TGF-β2: χ2=5.762, P=0.016; miR-450b-5p: χ2=13.267, P<0.001; miR-1283: χ2=19.431, P<0.001; miR-3671: χ2=8.131, P=0.004).

Conclusion: Current model combining tear miR-450b-5p, miR-1283, miR-3671, and TGF-β2 had important values in the identification of dry eye and was of great value in evaluating the risk of corneal injury.

Keywords: Analytes; Analytes, Clinical studies; Clinicalstudies; Enzymes; Proteins.

Potential of zebrafish as a model to characterise MicroRNA profiles in mechanically mediated joint degeneration

Mechanically mediated joint degeneration and cartilage dyshomeostasis is implicated in highly prevalent diseases such as osteoarthritis. Increasingly, MicroRNAs are being associated with maintaining the normal state of cartilage, making them an exciting and potentially key contributor to joint health and disease onset. Here, we present a summary of current in vitro and in vivo models which can be used to study the role of mechanical load and MicroRNAs in joint degeneration, including: non-invasive murine models of PTOA, surgical models which involve ligament transection, and unloading models based around immobilisation of joints or removal of load from the joint through suspension. We also discuss how zebrafish could be used to advance this field, namely through the availability of transgenic lines relevant to cartilage homeostasis and the ability to accurately map strain through the cartilage, enabling the response of downstream MicroRNA targets to be followed dynamically at a cellular level in areas of high and low strain.

Keywords: Cartilage; Joints; Loading; MicroRNA; Osteoarthritis; Zebrafish.

MicroRNA-23b-3p promotes pancreatic cancer cell tumorigenesis and metastasis via the JAK/PI3K and Akt/NF-κB signaling pathways

MicroRNA (miR)-23b-3p plays an important role in tumor growth, proliferation, invasion and migration in pancreatic cancer (PC). However, the function and mechanistic role of miR-23b-3p in the development of PC remains largely unknown. In the present study, the miR-23b-3p levels in the serum of patients with PC were found to be elevated, and the phosphorylation levels of Janus kinase (JAK)2, PI3K, Akt and NF-κВ were found to be upregulated. In addition, miR-23b-3p was induced in response to interleukin-6 (IL-6), which is known to be involved in the progression of PC. Overexpression of miR-23b-3p, on the other hand, activated the JAK/PI3K and Akt/NF-κB signaling pathways in PC cells, as evidenced by miR-23b-3p-induced upregulation of phosphorylated (p-)JAK2, p-PI3K, p-Akt and p-NF-κВ, as well as the downregulation of PTEN; and these effects were found to be reversible by miR-23b-3p inhibition. Furthermore, miR-23b-3p was found to downregulate PTEN by directly targeting the 3′-untranslated region of PTEN mRNA. Notably, in an in vivo xenograft mouse model, overexpression of miR-23b-3p accelerated PC cell-derived tumor growth, activated the JAK/Akt/NF-κВ signaling pathway and promoted liver metastasis. In contrast, knockdown of miR-23b-3p suppressed tumor growth and metastasis as well as JAK/Akt/NF-κВ signaling activity. In vivo imaging of the mice further confirmed the metastasis promoting role of miR-23b-3p in PC. These results suggested that miR-23b-3p enhances PC cell tumorigenesis and metastasis, at least, partially via the JAK/PI3K and Akt/NF-κB signaling pathways. Therefore, targeting miR-23b-3p or the JAK/PI3K and Akt/NF-κB signalings may be potential therapeutic strategy against PC.

Keywords: PTEN; interleukin-6/Janus kinase/Akt/NF-κВ; metastasis; miR-23b-3p; pancreatic cancer.

Long intergenic non-protein coding RNA-467 targets microRNA-451a in human colorectal cancer

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are frequently overexpressed in colorectal cancer (CRC). However, few related lncRNA signatures have been established for predicting CRC metastasis. The purpose of the present study was to identify lncRNAs that serve key roles in the metastasis of human CRC, and their potential downstream targets. A total of 31 human CRC biopsy samples were collected, and the expression of long intergenic non-protein coding RNA-467 (linc00467) and its association with clinical characteristics were evaluated. Consequently, linc00467 was revealed to be overexpressed in human CRC tissues, and its expression was significantly associated with metastasis and Tumor-Node-Metastasis stage. In HT29 and HCT116 cells, linc00467-knockout was revealed to decrease cellular proliferation and increase apoptosis (P<0.05). Finally, the downstream target of linc00467 in CRC promotion was predicted using bioinformatics analysis. The results demonstrated that linc00467 targets and regulates the expression of microRNA (miR)-451a, promoting carcinogenesis and metastasis in CRC. In conclusion, the results of the present study indicate that increased linc00467 expression promotes metastasis by targeting miR-451a, which ultimately increases cellular proliferation and inhibits apoptosis in human CRC cells.

Keywords: apoptosis; colorectal cancer; linc00467; metastasis; miR451a.

Downregulation of microRNA-320a inhibits proliferation and induces apoptosis of retinoblastoma cells via targeting TUSC3

MicroRNA (miR)-320a is specific to vertebrates and has been indicated to serve a role in a number of cancer types, such as gastric, colorectal, pancreatic and ovarian cancer. miR-320a has been reported to be expressed at high levels in retinoblastoma tissues; however its role and mechanism of function in retinoblastoma remain to be elucidated. The aim of the present study was to investigate the role of miR-320a in retinoblastoma cells and the underlying mechanisms. The expression of miR-320a in retinoblastoma cell lines Y79 and WERI-Rb-1, and normal human retinal pigment epithelial cell line ARPE-19 was examined via reverse transcription-quantitative PCR (RT-qPCR). TargetScan bioinformatics analysis and dual-luciferase reporter assay were used to predict and reveal the target gene of miR-320a. Target gene expression was detected via RT-qPCR in retinoblastoma cell lines and ARPE-19 cells. Subsequently, gain- or loss-of-function experiments for miR-320a and tumor suppressor candidate 3 (TUSC3) were performed to study the role of miR-320a/TUSC3 in retinoblastoma cells. Cell viability and apoptosis were assessed via MTT and flow cytometry analysis, respectively. Compared with ARPE-19 cells, miR-320a was prominently expressed in retinoblastoma cell lines. TUSC3 was predicted to be a target gene of miR-320a. Compared with ARPE-19 cells, the expression of TUSC3 in retinoblastoma cell lines was reduced. The results of MTT and flow cytometry analysis revealed that overexpression of TUSC3 reduced the viability of retinoblastoma cells and induced apoptosis. Additional analysis indicated that miR-320a inhibitor enhanced the expression of the target gene TUSC3, thereby inhibiting retinoblastoma cell viability and inducing apoptosis. The effects of miR-320a inhibitor on retinoblastoma cells were inhibited by TUSC3-short hairpin RNA. miR-320a regulated the viability and apoptosis of retinoblastoma cells via targeting TUSC3. Therefore, the present study provided a reference for investigating a potential target for the clinical treatment of retinoblastoma.

Keywords: apoptosis; microRNA-320a; proliferation; retinoblastoma; tumor suppressor candidate 3.

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