Farui Sun

Bio: Farui Sun is an academic researcher from Wuhan University of Science and Technology. The author has contributed to research in topics: Akt/PKB signaling pathway & PI3K/AKT/mTOR pathway. The author has an hindex of 2, co-authored 4 publications receiving 9 citations.

LINC00319 promotes osteosarcoma progression by regulating the miR‐455‐3p/NFIB axis

Abstract: Background Numerous studies have shown that aberrant expression of long non-coding RNAs (lncRNAs) is associated with the development and metastasis of osteosarcoma (OS). However, the role and function of LINC00319 with respect to regulating OS progression is unknown. The present study aimed to reveal the function and related mechanism of LINC00319 in OS. Methods The expression of LINC00319, miR-455-3p and nuclear factor IB (NFIB) in OS cells and tissues was determined using a reverse transcriptase-polymerase chain reaction (PCR). The sublocalization of LINC00319 was predicted by the lncATLAS database (http://lncatlas.crg.eu) and RNA fluorescence in situ hybridization (FISH) was further performed to detect the subcellular localization of LINC00319. LINC00319, miR-455-3p and NFIB target sites were predicted by StarBase (http://starbase.sysu.edu.cn/index.php) and validated using a dual luciferase reporter gene assay. We subsequently performed LINC00319 gain- and loss-of-function studies to define the role of LINC00319 in OS cell migration. Results PCR results showed that lncRNA LINC00319 exhibited high expression in tumor cells and tissue. Moreover, LINC00319 was positioned in the cytoplasm, which was identified by FISH. Knockdown of lncRNA LINC00319/NFIB or overexpression of miR-455-3p blocked the migration of OS cells. In addition, the inhibitory effect of migration with the knockdown of lncRNA LINC00319 was partially blocked by administration of miR-455-3p inhibitor. Conclusions lncRNA LINC00319 may promote OS progression by regulating the miR-455-3p/NFIB axis, which probably serves as an innovative potential indicator of prognosis and a target of therapy for OS.

PENK inhibits osteosarcoma cell migration by activating the PI3K/Akt signaling pathway

Abstract: This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration. A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting. Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration. PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.

Circular RNA circFOXP1 promotes angiogenesis by regulating microRNA -127-5p/CDKN2AIP signaling pathway in osteosarcoma.

Abstract: Osteosarcoma is known to have a high metastatic potential, which is closely related to angiogenesis. circRNAs are closely associated with osteosarcoma metastasis. This study aims to investigate the role of Circular RNA circFOXP1 in angiogenesis in osteosarcoma. We detected circFOXP1 expression in osteosarcoma, as well as its prognostic value. Tube formation assay and immunohistochemistry staining were conducted to determine the condition of tube formation. RT-qPCR was performed to explore targeted genes. Luciferase reporter assays were carried out to explore the interaction between miR-127-5p, ircFOXP1, and CDKN2AIP, respectively. In vivo studies further confirmed the relationship between circFOXP1 and tumor angiogenesis in osteosarcoma. We found that circFOXP1 expression was increased in osteosarcoma, and could promote angiogenesis in osteosarcoma through upregulating CDKN2AIP expression. Moreover, circFOXP1 could directly bind to miR-127-5p, which further targets CDKN2AIP directly. In conclusion, circFOXP1 promoted angiogenesis by regulating miR-127-5p/CDKN2AIP signaling pathway in osteosarcoma.

Overexpression of CRABP2 inhibits dexamethasone-induced apoptosis in human osteoblast cells.

Abstract: The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis.

Abstract: Circular RNAs (circRNAs) are a new class of RNAs that play an important role in the development of various tumors. However, the expression profile and biological function of circRNAs in osteosarcoma (OS) progression remain unclear. OS-related circRNA expression profiles from the GEO database (GSE96964) were downloaded to identify differentially expressed circRNAs between OS and normal tissues. We identified one upregulated circRNA (Circ-XPR1), and RT-PCR was performed to further confirm the expression abundance in OS tissue. Circ-XPR1 was closely related to overall survival and disease-free survival of OS patients. Knockdown of Circ-XPR1 significantly reduced the proliferation of OS cells. Gain- and loss-of-function studies showed that Circ-XPR1 promoted OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Our findings suggested that Circ-XPR1 regulates OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Therefore, the Circ-XPR1/miR-214-5p/DDX5 axis may serve as a potential therapeutically relevant target for OS.

Cadherin-11 cooperates with inflammatory factors to promote the migration and invasion of fibroblast-like synoviocytes in pigmented villonodular synovitis.

Abstract: Rationale: Pigmented villonodular synovitis (PVNS) is a destructive benign tumor-like hyperplastic disease that occurs in synovial tissue. Fibroblast-like synoviocytes (FLS) are the predominant cell type comprising the structure of the PVNS synovial lining layer. Due to a high recurrence rate, high invasion, migration, and cartilage destruction ability, PVNS causes substantial damage to patients and the efficacy of surgical resection is not satisfactory. Therefore, exploring the pathogenesis and identifying novel therapeutic targets for PVNS are urgently required. Currently, the pathogenesis of PVNS remains unclear, and there is uncertainty and controversy regarding whether PVNS is an inflammatory or a neoplastic disease. Cadherin-11 is a classical molecule that mediates hemophilic cell-to-cell adhesion in FLS and plays an important role in the normal synovium lining layer formation. This study aimed to explore the role of inflammation and cadherin-11 in PVNS pathogenesis and determine the effects of cadherin-11 as a molecular target for PVNS treatment. Methods: FLS were primarily cultured from PVNS patients during arthroscopic synovectomy. The level of cytokines in the PVNS synovial fluid was evaluated using a human antibody array. Cadherin-11 expression of PVNS FLS was detected by qPCR, Western blots, tissue immunohistochemistry, and cell immunofluorescence. Cadherin-11 was down-regulated by siRNA or up-regulated with a plasmid, with or without inflammatory factor stimulation, and PI3K/Akt was inhibited with LY294002. The capacity of migration and invasion of PVNS FLS was tested using Transwell and wound-healing assays. Activation of the nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was detected by Western blots. Chondrocyte damage by PVNS FLS was assessed with a co-culture assay. Results: Inflammatory factors (IL-1β and TNF-α) in the synovial fluid of PVNS patients were significantly up-regulated. Cadherin-11 was highly expressed in the FLS of PVNS patients, and positively correlated with recurrence, extra-articular migration, and cartilage destruction of PVNS. Knocking down of cadherin-11 inhibited the migration and invasion of PVNS FLS. Moreover, inflammatory factors up-regulated the expression of cadherin-11, which activated the NF-κB and MAPK signaling pathways and led to cartilage destruction. Inhibition of cadherin-11 blocked IL-1β- and TNF-α-induced activation of the above pathways, migration and invasion of PVNS FLS, and damage of chondrocyte. In addition, the elevation of cadherin-11 expression, together with the migration and invasion, of PVNS FLS was down-regulated by the inhibition of the PI3K/Akt signaling pathway. Conclusions: Cadherin-11 plays an important role in the pathogenesis of PVNS and forms a positive feedback loop with inflammatory factors, which further activates the NF-κB and MAPK pathways to trigger an inflammatory cascade. Cadherin-11-mediated inflammation results in PVNS with high recurrence, invasiveness, and strong cartilage destruction ability, and eventually promotes the transformation of PVNS from the initial inflammatory disease to neoplastic disease. Thus, inhibition of cadherin-11 together with its related inflammatory reaction, represents a new therapeutic strategy for PVNS.

MicroRNA-138-5p targets the NFIB-Snail1 axis to inhibit colorectal cancer cell migration and chemoresistance.

Abstract: Colorectal cancer ranks among the most lethal diseases worldwide. Although much progress has been made in research and treatment of colorectal cancer in recent years, the underlying mechanisms related to migration of the cancer cells and the reason for chemoresistance still remain unclear. In this research, we explored the underlying effect of miR-138-5p in colorectal cancer. We used qRT-PCR to investigate the expression of miR-138-5p, Snail1, NFIB in colorectal cancer cells. Lentiviral vectors containing miR-138-5p mimics and inhibitors were constructed and transfected cells. Wound healing assay was applied to illustrate interferences on cell migration. Fluorouracial, doxorubicin, cisplat in were used to detect chemotherapy resistance. In order to identify target genes, bioinformatic methods were applied. Snail1 and NFIB protein expression in stable cell lines was detected using Western blot. Double luciferase and CHIP experiment were used to verify binding sites. We used rescue experiments to further explore the interactions among Snail1, NFIB and miR-138-5p. The expression of miR-138-5p in colorectal cancer cells was low. miR-138-5p inhibited cell migration in colorectal cancer, and could negatively regulate chemotherapy resistance. miR-138-5p targeted NFIB, and regulated Snail1 expression, which mediated colorectal cancer cell migration and chemotherapy resistance. Our research indicates that miR-138-5p could be a crucial modulator controlling colorectal cancer cell migration and chemoresistance, by acting upon the NFIB-Snail1 axis. miR-138-5p has an emerging prospect to be exploited as a new target for colorectal cancer.

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

Abstract: Circular RNAs (circRNAs), a class of new endogenous non-coding RNAs (ncRNAs), are closely related to the carcinogenic process and play a critical role in tumor metastasis. CircRNAs can lay the foundation for tumor metastasis via promoting tumor angiogenesis, make tumor cells gain the ability of migration and invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, and other non-cellular components in the tumor microenvironment, damage the normal immune function or escape the immunosuppressive network, and further promote cell survival and metastasis. Herein, based on the characteristics and biological functions of circRNA, we elaborated on the effect of circRNA via circRNA-associated competing endogenous RNA (ceRNA) network by acting as miRNA/isomiR sponges on tumor angiogenesis, cancer cell migration and invasion, and interaction with the tumor microenvironment (TME), then explored the potential interactions across different RNAs, and finally discussed the potential clinical value and application as a promising biomarker. These results provide a theoretical basis for the further application of metastasis-related circRNAs in cancer treatment. In summary, we briefly summarize the diverse roles of a circRNA-associated ceRNA network in cancer metastasis and the potential clinical application, especially the interaction of circRNA and miRNA/isomiR, which may complicate the RNA regulatory network and which will contribute to a novel insight into circRNA in the future.