lncRNA MEG3 modified epithelial-mesenchymal transition of ovarian cancer cells by sponging miR-219a-5p and regulating EGFR

This study was aimed to verify whether there existed any associations between long noncoding RNA MEG3/miR-219a-5p/EGFR axis and the development of ovarian cancer (OC). As a whole, we gathered 317 pairs of OC tissues and surgical marginal normal tissues and simultaneously acquired four OC cell lines (ie, A2780, Caov-3, OVCAR-3, and SKOV-3) and human normal ovarian surface epithelial cell line. Moreover, pcDNA3.1-MEG3, si-MEG3, miR-219a-5p mimic, miR-219a-5p inhibitor, pcDNA3.1-EGFR, and si-EGFR were, respectively, transfected into the OC cells, and their impacts on viability, proliferation, apoptosis, invasion, and migration of OC cells were assessed via conduction of MTT assay, colony formation assay, flow cytometry assay, transwell assay, and scratch assay. Ultimately, dual-luciferase reporter gene assay was performed to testify the targeted relationships among maternally expressed gene 3 (MEG3), miR-219a-5p, and estimated glomerular filtration rate (EGFR). It was indicated that underexpressed MEG3 and miR-219a-5p were significantly associated with unfavorable prognosis of patients with OC when compared with overexpressed MEG3 and miR-219a-5p (P < .05). In addition, the OC cells transfected with si-MEG3 or miR-219a-5p inhibitor exhibited stronger viability, proliferation, invasion, and migration than untreated cells (P < .05). Correspondingly, the apoptotic percentage of OC cells was reduced observably under treatments of si-MEG3 and miR-219a-5p inhibitor (P < .05). Moreover, MEG3 exerted modulatory effects on the expression of miR-219a-5p (P < .05), and there was a sponging relationship between them (P < .05). Finally, EGFR expression was modified by both MEG3 and miR-219a-5p significantly (P < .05), and raising EGFR expression could changeover the impacts of MEG3 and miR-219a-5p on the above-mentioned activity of OC cells (P < .05). Conclusively, MEG3 could serve as a promising biomarker for diagnosis and treatment of OC, considering its involvement with OC etiology via regulation of miR-219a-5p/EGFR axis.     

LncRNA BLACAT1 regulates VASP expression via binding to miR-605-3p and promotes giloma development

Glioma, an aggressive tumor in brain, presents a very poor prognosis. Emerging evidence has demonstrated that dysfunction of long noncoding RNAs (lncRNAs) is closely related to giloma development. However, the roles of lncRNA BLACAT1 in glioma are not unknown. In this study, we utilized in vitro and in vivo experiments to explore the effects of BLACAT1 on glioma cells. BLACAT1 levels were increased in glioma tissues. Upregulation of BLACAT1 showed poor prognosis. Silencing of BLACAT1 markedly repressed glioma proliferation, migration, and invasion, and suppressed glioma growth in vivo. We also illustrated that BLACAT1 worked as the sponge for miR-605-3p and promoted VASP expression. miR-605-3p was downregulated in glioma and repressed glioma proliferation, migration, and invasion. And VASP is upregulated and contributed to glioma progression. Summarily, this study highlights the important roles of BLACAT1/miR-605-3p/VASP axis in glioma progression.     

LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR-188-5p

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor-adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)-188-5p was downregulated in tumor tissues than in tumor-adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR-188-5p downregulated each other. PAPAS overexpression promoted, while miR-188-5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR-34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR-188-5p.     

LncRNA OIP5-AS1 regulates radioresistance by targeting DYRK1A through miR-369-3p in colorectal cancer cells

Object

This study aimed to investigate the role of lncRNA OIP5-AS1 in regulating radioresistance of colorectal cancer (CRC) cells.

Fibronectin-1 modulated by the long noncoding RNA OIP5-AS1/miR-200b-3p axis contributes to doxorubicin resistance of osteosarcoma cells

Chemoresistance has been an obstacle in the further improvement of 5-year survival rates of osteosarcoma (OS) patients, but the underlying mechanism of chemo-resistance remains unclear. A comprehensive analysis of mRNAs and noncoding RNAs related to OS chemo-resistance could help solve this problem. In the current study, we first identified that fibronectin-1 (FN1), screened by microarray analysis in three paired chemo-resistant and chemo-sensitive OS cell lines, was significantly upregulated in the chemo-resistant OS cell lines and tissues and was related to unfavourable prognosis. Further functional assays revealed that FN1 inhibition greatly increased the sensitivity of OS cells to doxorubicin in vitro and in vivo, whereas FN1 overexpression had the opposite effect. Moreover, mechanistic investigation demonstrated, by a series of assays that included luciferase reporter gene, RNA immunoprecipitation, RNA pull-down and rescue assays, that FN1 expression was regulated by the oncogenic long noncoding RNA (lncRNA) OIP5-AS1 through sponging miR-200b-3p. Thus, these results indicated the role and potential application of the lncRNA OIP5-AS1/miR-200b-3p/FN1 regulatory pathway as a promising target in treatment of OS chemo-resistance.     

Exosomal miR-21-5p derived from bone marrow mesenchymal stem cells promote osteosarcoma cell proliferation and invasion by targeting PIK3R1

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can release a large number of exosomes which act as paracrine mediators in tumour-associated microenvironment. However, the role of MSC-derived exosomes in pathogenesis and progression of cancer cells especially osteosarcoma has not been thoroughly clarified until now. In this study, we established a co-culture model for human bone marrow-derived MSCs with osteosarcoma cells, then extraction of exosomes from induced MSCs and study the role of MSC-derived exosomes in the progression of osteosarcoma cell. The aim of this study was to address potential cell biological effects between MSCs and osteosarcoma cells. The results showed that MSC-derived exosomes can significantly promote osteosarcoma cells’ proliferation and invasion. We also found that miR-21-5p was significantly over-expressed in MSCs and MSC-derived exosomes by quantitative real-time polymerase chain reaction (qRT-PCR), compared with human foetal osteoblastic cells hFOB1.19. MSC-derived exosomes transfected with miR-21-5p could significantly enhance the proliferation and invasion of osteosarcoma cells in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter gene assays validated the targeted relationship between exosomal miR-21-5p and PIK3R1; we further demonstrated that miR-21-5p-abundant exosomes derived human bone marrow MSCs could activate PI3K/Akt/mTOR pathway by suppressing PIK3R1 expression in osteosarcoma cells. In summary, our study provides new insights into the interaction between human bone marrow MSCs and osteosarcoma cells in tumour-associated microenvironment.     

miR-17-5p promotes proliferation and epithelial-mesenchymal transition in human osteosarcoma cells by targeting SRC kinase signaling inhibitor 1

MicroRNA-17-5p (miR-17-5p) and epithelial-mesenchymal transition (EMT) have been reported to participate in the development and progression of multiple cancers. However, the relationship between the miR-17-5p and EMT in osteosarcoma (OS) is still poorly understood. This study was to investigate the effects of the miR-17-5p and its potential mechanism in regulating proliferation, apoptosis, and EMT of human OS. Quantitative real-time PCR was used to detect the miR-17-5p and SRC kinase signaling inhibitor 1 (SRCIN1) messenger RNA expression in OS specimens and cell lines. After transfection with miR-17-5p inhibitors, proliferation, apoptosis, migration, and invasion of OS cells were assessed by using the Cell Counting Kit-8, the annexin V-FITC apoptosis, wound-healing, and transwell assays. The SRCIN1 was validated as a target of the miR-17-5p through bioinformatics algorithms and luciferase reporter assay. Moreover, the expression of EMT markers, E-cadherin, N-cadherin, and Snail was identified by the Western blot analysis. MiR-17-5p was significantly upregulated in OS tumor samples and cell lines. It inhibited proliferation and EMT, and promoted apoptosis in OS. The SRCIN1 was identified as a direct target of the miR-17-5p. Silenced miR-17-5p could change the expression of EMT markers, such as upregulating the expression of E-cadherin, and downregulating the expression of N-cadherin and Snail through targeting the antioncogenic SRCIN1. These findings suggest that the miR-17-5p promotes cell proliferation, and EMT in human OS by directly targeting the SRCIN1, and reveal a branch of the miR-17-5p/SRCIN1/EMT signaling pathway involved in the progression of OS.     

MiR-186-5p通过靶向调控PTTG1抑制肺腺癌细胞的上皮-间质转化

先前研究表明,miR-186-5p在人类许多恶性肿瘤中扮演抑癌基因的作用,但其在肺腺癌上皮-间质转化（epithelial-mesenchymal transition,EMT）中的作用并不明确。本研究旨在证明,miR-186-5p可通过靶向调控PTTG1抑制肺腺癌细胞的上皮-间质转化。我们首先分析了miR-186-5p在人肺癌细胞中的表达。荧光定量PCR（QRT-PCR）结果显示,与人正常肺上皮细胞BEAS-2B相比,肺腺癌细胞SPC-A1、A549中的miR-186-5p表达量明显降低。为研究miR-186-5p在肺腺癌细胞中的功能,利用GV369-miR-186-5p表达载体,实现了在A549细胞中的过表达。基因转染结合Transwell侵袭结果显示,与对照质粒转染的A549细胞相比,过表达miR-186-5p的A549细胞的体外侵袭能力明显下降。Western印迹检测细胞中EMT相关标志物揭示,GV369-miR-186-5p转染的A549细胞中的上皮-钙黏着蛋白（E-cadherin）表达明显上调,而神经-钙黏着蛋白（N-cadherin）和波形蛋白（vimentin）表达明显下调。同时,GV369-miR-186-5p转染引起其靶基因--垂体肿瘤转化基因1（pituitary tumor-transforming gene 1,PTTG1）编码蛋白在A549细胞中明显降低。重要的是,过表达miR-186-5p与敲减PTTG1均可导致上皮-钙黏着蛋白表达上调,而神经-钙黏着蛋白和波形蛋白下调|而miR-186-5p和PTTG1表达载体共转染后,3种EMT相关标志物在A549的表达与对照细胞的表达无明显差异,提示过表达PTTG1可抵消miR-186-5p对EMT相关标志物表达的影响。综上所述,miR-186-5p可通过靶向调控PTTG1抑制EMT的发生,进而抑制肺腺癌细胞的侵袭转移。     

LncRNA MALAT1 targeting miR-124-3p regulates DAPK1 expression contributes to cell apoptosis in Parkinson's Disease

Death associated protein kinase 1 (DAPK1) was initially discovered in the progress of gamma-interferon induced programmed cell death, it is a key factor in the central nervous system, including Parkinson's disease (PD). However, the underlying mechanisms of DAPK1 in PD remain unclear and this research work aims to explore the potential mechanisms of DAPK1 in PD. In the study, we exposed SH-SY5Y cells to MPP⁺ and treated mice with MPTP to investigate the roles of DAPK1 in PD and the underlying mechanisms. The results indicated that the expression of DAPK1 is significantly upregulated and negatively correlated with miR-124-3p levels in SH-SY5Y cells treated by MPP⁺, and miR-124-3p mimics could effectively inhibit DAPK1 expressions and alleviate MPP⁺-induced cell apoptosis. In addition, knockdown MALAT1 reduces the levels of DAPK1 and the ratio of SH-SY5Y cell apoptosis, which is reversed via miR-124-3p inhibitor in vitro. Similarly, knockdown MALAT1 could improve behavioral changes and reduce apoptosis by miR-124-3p upregulation and DAPK1 downregulation in MPTP induced PD mice. Taken together, our data showed that lncRNA MALAT1 positively regulates DAPK1 expression by targeting miR-124-3p, and mediates cell apoptosis and motor disorders in PD. In summary, these results suggest that MALAT1/miR-124-3p /DAPK1 signaling cascade mediates cell apoptosis in vitro and in vivo, which may provide experimental evidence of developing potential therapeutic strategies for PD.     

miR-142-3p/5p role in cancer: From epigenetic regulation to immunomodulation

MicroRNAs (miRNAs) play critical roles in cancer pathobiology, acting as regulators of gene expression and pivotal drivers of tumorigenesis. It is believed that miRNAs act through canonical mechanisms, involving the binding of mature miRNAs to target messenger RNAs (mRNAs) and subsequent repression of protein translation or degradation of target mRNAs. miR-142-3p/5p has been extensively studied and established as a key regulator in various malignancies. Recent discoveries have revealed miR-142-3p/5p serve as either oncogene or tumor suppressor in cancer. By targeting epigenetic factor and cancer-related signaling pathway, miR-142-3p/5p can regulate wide range of downstream genes. The immune modulatory role of miR-142-3p/5p has been shown in various cancers, which provides significant insight into immunosuppression and tumor escape from the immune response. Exosomes with miR-142-3p/5p facilitate cell communication and can affect cancer cell behavior, offering potential therapeutic, and diagnosis applications in cancer therapy. In this review, for the first time, we comprehensively summarize the current knowledge regarding mentioned functions of miR-142-3p/5p in cancer pathobiology.     

LncRNA-UCA1 modulates progression of colon cancer through regulating the miR-28-5p/HOXB3 axis

Emerging evidence has shown that the long noncoding RNA urothelial carcinoma–associated 1 (UCA1) plays a tumor-promoting role in colorectal cancer, while miR-28-5p shows tumor-inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR-28-5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR-28-5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR-28-5p. We also, for the first time, identified HOXB3 as the target gene of miR-28-5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR-28-5p/HOXB3 in colon cancer, suggesting that UCA1, miR-28-5p, and HOXB3 are the potential targets for colon cancer therapy.