scholarly journals MicroRNA-106b Overexpression Suppresses Synovial Inflammation and Alleviates Synovial Damage in Patients with Rheumatoid Arthritis

2021 ◽  
Author(s):  
Linchen Liu ◽  
Haiyan Chen ◽  
Ting Jiang ◽  
Dongyi He
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Pearson Correlation ◽  
Negative Control ◽  
Synovial Inflammation ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Qrt Pcr ◽  
Synovial Tissues

Abstract Objectives To explore the effect of miR-106b on synovial inflammation and damage in rheumatoid arthritis (RA) patients, and further to investigate its possible mechanism. Methods : Quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, in situ hybridization and immunohistochemistry assay were separately used to verify the levels of miR-106b and cytokines in the synovial tissues of patients with RA or osteoarthritis (OA). Pearson correlation analysis was conducted to examine the bivariate relationship between miR-106b and cytokines or RANKL. Following the isolation and culture of fibroblast-like synoviocytes (FLS), the cells were transfected with lentivirus-mediated miR-106b mimic, miR-106b inhibitor, and negative control miR-106b mimic, respectively. Thereafter, cell proliferation was measured by Cell Counting Kit-8 assay, and cell invasion and migration capacity was assessed by Transwell assay. Furthermore, concentration and expression of cytokines were separately detected by Enzyme linked immunosorbent assay and Western blot. Results Compared with osteoarthritis, validation by qRT-PCR showed that RA patients had a lower level of miR-106b and higher levels of receptor activator of nuclear factor-κ B ligand (RANKL), tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). Additionally, the scatter plot showed that the relative transcription of miR-106b level was negatively correlated to the level of TNF-a, IL-6, and RNKAL in the synovial tissues of both RA and OA patients (All P<0.05). Furthermore, miR-106b overexpression suppressed cell proliferation, migration and invasion capacity of human RA-FLS. Conclusions miR-106b overexpression suppresses synovial inflammation and alleviates synovial damage, thus it may be served as a potential therapeutic target for RA patients.

scholarly journals Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Qu ◽  
Ling Jiang ◽  
Guanhua Hou
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Western Blotting ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mesenchymal Transition ◽  
Synovial Tissues

Abstract Background Circular RNAs (circRNAs) are associated with rheumatoid arthritis (RA) development. The purpose of this study is to explore the function and mechanism of circRNA fragile mental retardation 2 (circ-AFF2) in the processes of rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). Methods Circ-AFF2, microRNA (miR)-650, and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) levels were determined in synovial tissues of RA and RAFLSs by quantitative reverse transcription polymerase chain reaction or Western blotting. Cell proliferation, inflammatory response, apoptosis, caspase3 activity, migration, invasion, and epithelial-mesenchymal transition (EMT) were investigated using Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), flow cytometry, Transwell, and Western blotting analyses. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and pull-down assays were performed to assess the binding relationship. Results Circ-AFF2 expression level was enhanced in synovial tissues of RA and RAFLSs. Circ-AFF2 overexpression facilitated cell proliferation, inflammatory response, migration, invasion, and EMT and repressed apoptosis in RAFLSs. Circ-AFF2 downregulation played an opposite role. Circ-AFF2 targeted miR-650, and miR-650 downregulation reversed the effect of circ-AFF2 interference on RAFLS processes. CNP was targeted by miR-650, and circ-AFF2 increased CNP expression by regulating miR-650. MiR-650 overexpression constrained cell proliferation, inflammatory response, migration, invasion, and EMT and contributed to apoptosis by decreasing CNP in RAFLSs. Conclusion Circ-AFF2 promoted proliferation, inflammatory response, migration, and invasion of RAFLSs by modulating the miR-650/CNP axis.

scholarly journals Lnc RNA ZFAS1 regulates the proliferation, apoptosis, inflammatory response and autophagy of fibroblast-like synoviocytes via miR-2682-5p/ADAMTS9 axis in rheumatoid arthritis

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Shanshan Yang ◽  
Wei Yin ◽  
Yan Ding ◽  
Fan Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Large Subunit ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Behaviors ◽  
Synovial Tissues ◽  
Related Proteins ◽  
Fibroblast Like Synoviocytes

Abstract Backgrounds: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated. Methods: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay. Results: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA. Conclusion: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.

scholarly journals Lnc BACE1-AS Promotes The Progression of Osteosarcoma Through miR-762/SOX7 Axis

2021 ◽  
Author(s):  
qu yanlong ◽  
Wang Chunlei ◽  
Zhang Tao ◽  
Yang Li ◽  
Na Xinyu
Keyword(s):  
Cell Proliferation ◽  
Binding Sites ◽  
Molecular Basis ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Lower Expression ◽  
Geo Database

Abstract Background: Osteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting bone that occurs in adolescents and children. LncRNAs are important regulators of tumorigenesis and development. This study aimed to explore the role and molecular basis of LncRNA BACE1-AS in OS. Methods and results : Through the analysis of differential expressed lncRNAs in OS tissues by GEO database, LncRNA BACE1-AS displayed a remarkably lower expression. This found could also be observed in both OS tissues and cell lines by qRT-PCR. Furthermore, using Cell counting kit-8 (CCK-8), transwell, wound healing and westernblot assays, overexpression LncRNA BACE1-AS remarkably reduced cell proliferation, migration and invasion abilities in OS. In addition, LncRNA BACE1-AS was validated as a sponge of miR-762 through the prediction of lncRNASNP. Further, luciferase reporter and RIP assays were conducted to confirm the binding sites between LncRNA BACE1-AS and miR-762. SOX7 was a target of miR-762 and could be regulate by LncRNA BACE1-AS. Moreover, inhibition of miR-762 could attenuate the role of sh-LncRNA BACE1-AS in OS cells, at meanwhile reduced the expression of SOX7. Conclusion : In this study, LncRNA BACE1-AS regulated proliferation, migration, invasion and apoptosis of OS cells by miR-762/SOX7 axis, implying that LncRNA BACE1-AS was a potential target for OS therapy.

scholarly journals Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

2018 ◽  
Vol 51 (3) ◽  
pp. 1364-1375 ◽  
Author(s):  
Dan Fei ◽  
Xiaona Zhang ◽  
Jinxiang Liu ◽  
Long Tan ◽  
Jie Xing ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Colony Formation ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr

Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

scholarly journals CircMAPK9 promotes the progression of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-140-3p/PPM1A axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhihuan Luo ◽  
Shaojian Chen ◽  
Xiaguang Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Western Blot ◽  
Joint Disease ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blot Assay ◽  
Fibroblast Like Synoviocytes

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, and fibroblast-like synoviocytes (FLSs) are key effector cells in RA development. Mounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of RA. However, the precise mechanism of circRNA mitogen-activated protein kinase (circMAPK9) in the cell processes of FLSs has not been reported. Methods The expression levels of circMAPK9, microRNA-140-3p (miR-140-3p), and protein phosphatase magnesium-dependent 1A (PPM1A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cell migration and invasion were tested by transwell assay. All the proteins were inspected by western blot assay. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-140-3p and circMAPK9 or PPM1A was verified by dual-luciferase reporter assay. Results CircMAPK9 and PPM1A were upregulated and miR-140-3p was downregulated in RA patients and FLSs from RA patients (RA-FLSs). CircMAPK9 silence suppressed cell proliferation, migration, invasion, inflammatory response, and promoted apoptosis in RA-FLSs. MiR-140-3p was a target of circMAPK9, and miR-140-3p downregulation attenuated the effects of circMAPK9 knockdown on cell progression and inflammatory response in RA-FLSs. PPM1A was targeted by miR-140-3p, and circMAPK9 could regulate PPM1A expression by sponging miR-140-3p. Furthermore, miR-140-3p could impede cell biological behaviors in RA-FLSs via targeting PPM1A. Conclusion CircMAPK9 knockdown might inhibit cell proliferation, migration, invasion, inflammatory response, and facilitate apoptosis in RA-FLSs via regulating miR-140-3p/PPM1A axis, offering a new mechanism for the comprehension of RA development and a new insight into the potential application of circMAPK9 in RA treatment.

scholarly journals MiRNA-506 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targetting TLR4

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Dan Li ◽  
Qingchen Zhou ◽  
Gaojian Hu ◽  
Gang Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Qrt Pcr ◽  
Cycle Arrest ◽  
Tnf Α ◽  
Proliferation And Apoptosis ◽  
Synovial Tissues ◽  
Induced Apoptosis ◽  
Fibroblast Like Synoviocytes

Abstract Fibroblast-like synoviocytes (FLSs) play a crucial role in rheumatoid arthritis (RA) pathogenesis. While miRNA (miR)-506 has been implicated in the progression of multiple diseases, its role in RA remains to be explored. The present study evaluated the function of miR-506 in the regulation of RA-FLSs. FLSs were prepared from RA and healthy synovial tissues. The expression of miR-506 was measured by quantitative real time PCR (qRT-PCR). The effects of miR-506 on RA-FLSs proliferation and apoptosis were detected by cell counting Kit-8 and flow cytometry assays, respectively. The determination of TNF-α, IL-6, and IL-1β concentrations in RA-FLSs supernatant were done by ELISA. The levels of miR-506 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-506 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell cycle arrest at the G0/G1 phase. The overexpression of miR-506 induced apoptosis, along with an increase in activities of caspase-3 and -8. A target gene Toll-like receptor 4 (TLR4) under the direct regulation of miR-506 was identified through the luciferase assay, qRT-PCR and western blot analysis. Forced overexpression of TLR4 in the rescue experiments showed that TLR4 effectively reversed the effect on proliferation and apoptosis in miR-506-overexpressing RA-FLSs. Thus, miR-506 may be a potential target for RA prevention and therapy of RA.

scholarly journals MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Qiaofeng Wei ◽  
Fang Lv ◽  
Hongju Zhang ◽  
Xinfang Wang ◽  
Qin Geng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Biological Activities ◽  
Type Ii Collagen ◽  
Migration And Invasion ◽  
Luciferase Activity Assay ◽  
Prostaglandin Endoperoxide Synthase ◽  
Synovial Tissues ◽  
Relationship Of

Abstract Objective: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA. Methods: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay. Results: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2. Conclusion: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.

scholarly journals SP/NK-1R Axis Promotes Perineural Invasion of Pancreatic Cancer and is Affected by lncRNA LOC389641

2021 ◽  
Author(s):  
Tengfei Ji ◽  
Keqiang Ma ◽  
Hongsheng Wu ◽  
Tiansheng Cao#
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Perineural Invasion ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neurokinin 1 Receptor ◽  
Neurokinin 1

Abstract Background Pancreatic cancer is a deadly disease with low overall survival during the past 30 years. Perineural invasion (PNI) was considered to be the main reason for poor prognosis. In the present study, we analyzed the role of substance P (SP)/neurokinin-1 receptor (NK-1R) and long non-coding RNA (lncRNA) LOC389641 on pancreatic cancer PNI. Material and methods Pancreatic cancer cell lines of BxPC-3 and MIAPaCa-2 were co-cultured with SHSY5Y cells, and then stimulated with SP to simulate the in vivo influence of pancreatic cancer by ganglion. The co-culture cells were transfected with overexpressed neurokinin-1 receptor (NK-1R), silenced NK-1R, overexpressed LOC389641, and silenced LOC389641. Enzyme-linked immunosorbent assay (ELISA) assay was performed to examine the concentration of SP in cells. The cell proliferation ability was assessed by cell counting kit-8 and 5-ethynyl-2’-deoxyuridine (EdU) assays. The wound-healing and Transwell assays were carried out to determine the cell migration and invasion analyses. Quantitative real-time PCR (qRT-PCR), western blot, immunofluorescence (IF) analyses were performed to evaluate the expression levels. Results Addition of SP in co-culture system positively regulates cell proliferation, migration, and invasion of pancreatic cancer PNI. SP significantly stimulated NK-1R/Akt/NF-κB signaling pathway. The concentration of 100 nmol/L for 24h was chosen to be optimal for SP treatment.NK-1R positively regulated the proliferation, migration, and invasion of pancreatic cancer PNI. The expression of lncRNA LOC389641 and mRNA tumor necrosis factor receptor SF10A (TNFRSF10A) was not affected by SP. Overexpressed and silenced LOC389641 can correspondingly change the effect of SP stimulation on pancreatic cancer PNI. Conclusion We found that SP/NK-1R and LOC389641 promote the cell progression of pancreatic cancer PNI. Moreover, we assumed that the pancreatic cancer PNI promoted by SP/NK-1R axis may be blocked by the TNFRSF10A/NF-κB pathway mediated by LOC389641.

scholarly journals MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Beibei Zu ◽  
Lin Liu ◽  
Jingya Wang ◽  
Meirong Li ◽  
Junxia Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Pearson Correlation ◽  
Fibrous Tissue ◽  
Synovial Fibroblasts ◽  
Cell Counting ◽  
Sirtuin 3 ◽  
Fibrous Tissues

Abstract Background Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. Methods RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. Results Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. Conclusions The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

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