Signalling by the Platelet C-Type Lectin Receptor CLEC-2 Is Mediated by a Novel Mechanism Involving Syk and a Single YxxL Motif.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 381-381
Author(s):  
Andrew C. Pearce ◽  
Gemma L.J. Fuller ◽  
Katsue Suzuki-Inoue ◽  
Michael G. Tomlinson ◽  
Steve P. Watson
Keyword(s):  
Cell Lines ◽  
Transmembrane Protein ◽  
Mutant Cell ◽  
Consensus Sequence ◽  
Adaptor Proteins ◽  
Site Directed Mutagenesis ◽  
Luciferase Reporter ◽  
Tyrosine Residue ◽  
Lectin Receptor ◽  
Platelet Receptor

Abstract We have recently identified the C-type lectin-like receptor CLEC-2 as a novel receptor for the snake toxin rhodocytin on platelets. CLEC-2 is a 32 kDa type II transmembrane protein with a single cytoplasmic tyrosine residue in a YxxL consensus sequence. It is the first C-type lectin receptor that has been shown to activate platelets. The aim of the present study was to investigate the mechanism of signalling by CLEC-2 using model cell lines and to establish the role of the YxxL motif in this process. We have expressed CLEC-2 in wild type DT40 B cells and Jurkat T cells and in mutant derivatives of these cell lines that lack key signalling proteins. We have assayed PLCγ activation using an NFAT-luciferase reporter assay. Site directed mutagenesis of the cytoplasmic tyrosine residue of CLEC-2 has been used to assess its role in CLEC-2 signalling. We have compared the signalling pathway of CLEC-2 with that of the ITAM-coupled collagen receptor GPVI by expressing GPVI in the mutant cell lines and monitoring responses to the GPVI specific agonist convulxin as above. Cells transfected with CLEC-2 respond to rhodocytin. Mutation of the CLEC-2 YxxL motif to FxxL abrogates CLEC-2 signalling. CLEC-2 signalling is abrogated in cells deficient in Src or Syk family kinases or PLCγ . CLEC-2 signalling is partially dependent on Tec family kinases and the adaptors LAT and SLP-76/BLNK. Interestingly, GPVI signalling and CLEC-2 signalling show a differential requirement for the SLP-76 family adaptor proteins SLP-76 or Blnk; GPVI signalling is entirely dependent on SLP-76/Blnk, whereas CLEC-2 signalling is only partially dependent on these proteins. These observations are consistent with a model whereby CLEC-2 recruits Syk via its YxxL motif and initiates a signalling cascade similar to the major platelet glycoproteins GPVI and integrin α IIbβ 3. CLEC-2 is the first platelet receptor shown to regulate Syk through a single YxxL motif. Importantly, despite the similarity in the signalling proteins involved in signalling by the ITAM receptor, the integrin receptor and the C-type lectin receptor, the signalling pathways are organised and initiated differently.

Single-arm study of bimiralisib in head and neck squamous cell carcinoma (HNSCC) patients (pts) harboring NOTCH1 loss of function (LOF) mutations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6590-TPS6590
Author(s):  
Faye M. Johnson ◽  
Filip Janku ◽  
J. Jack Lee ◽  
Debora Schmitz ◽  
Henk Streefkerk ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Lines ◽  
Clonal Evolution ◽  
Mutant Cell ◽  
Objective Response ◽  
Site Directed Mutagenesis ◽  
Loss Of Function ◽  
Null Cell ◽  
Second Stage ◽  
Notch1 Mutations

TPS6590 Background: Effective targeted therapies are needed for HNSCC that is lethal despite recent advances with immunotherapy. A major challenge to personalize treatment is that most genomic alterations are in tumor suppressors, including NOTCH1 that is mutated in ~20% of HNSCC. We recently published that HNSCC cell lines harboring NOTCH1 LOF mutations undergo cell death in vivo and in vitro following PI3K inhibition, in contrast to PIK3CA mutant cell lines that merely undergo cell cycle arrest when exposed to the same drugs. Based on these results we initiated a novel genomic biomarker-driven phase II clinical trial treating NOTCH1 mutant HNSCC pts with the dual PI3K/mTOR inhibitor bimiralisib (PQR309). Methods: The primary objective is to determine the objective response rate (ORR) of recurrent/metastatic HNSCC harboring NOTCH1 LOF mutations to bimiralisib. Pts who have already received standard platinum chemotherapy and immunotherapy will receive bimiralisib orally twice per wk unless progression or intolerable toxicity occurs. Tumors will be evaluated using RECIST q 6 wks. A Simon’s optimal two-stage design is used. To have 80% power to detect an ORR of 30%, (one-sided α = 0.05, β = 0.20) 10 pts will be enrolled in the first stage. If ≤1 pts respond, the trial will be closed for futility. If ≥2 pts have an OR, the study will enroll an additional 19 pts in the second stage. The null hypothesis (ORR ≤ 10%) will be rejected if ≥ 6 in 29 pts have an OR. Seven pts have enrolled. The algorithm for determining NOTCH1 mutation function is based on the patterns of mutations in HNSCC vs. leukemia where mutations are activating. It may be difficult to determine whether NOTCH1 mutations are homo- or heterozygous due to normal cell contamination. Therefore, levels of activated NOTCH1 in pretreatment tumors may be assessed by IHC with an antibody against activated NOTCH1 (NICD). In parallel with the trial, to further confirm NOTCH1 LOF, we can use site-directed mutagenesis to re-create NOTCH1 mutations from trial pts that will then be introduced into NOTCH1-null cell lines to assay for NICD and growth inhibition with culture on NOTCH1 ligand. All pts will have serial collection of blood for pharmacokinetics and for ctDNA to examine clonal evolution associated with acquired resistance. Samples with high NOTCH1 mutation ctDNA VAF will be analyzed by WES and compared with pretreatment tissue. In the second stage, IHC and WES may be performed on pre- and post- treatment (day 15 and progression) tissue to examine pharmacodynamics and mechanisms of resistance. Clinical trial information: NCT03740100 .

Structural significance of the GTP-binding domain of ras p21 studied by site-directed mutagenesis

1987 ◽  
Vol 7 (9) ◽  
pp. 3092-3097
Author(s):  
D J Clanton ◽  
Y Y Lu ◽  
D G Blair ◽  
T Y Shih
Keyword(s):  
Cell Lines ◽  
Consensus Sequence ◽  
Point Mutations ◽  
Soft Agar ◽  
Binding Activity ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Gtp Binding ◽  
Nih 3T3 ◽  
Autokinase Activity

Point mutations of p21 proteins were constructed by oligonucleotide-directed mutagenesis of the v-rasH oncogene, which substituted amino acid residues within the nucleotide-binding consensus sequence, GXG GXGK. When the glycine residue at position 10, 13, or 15 was substituted with valine, the viral rasH product p21 lost its GTP-binding and autokinase activities. Other substitutions at position 33, 51, or 59 did not impair its binding activity. G418-resistant NIH 3T3 cell lines were derived by transfection with constructs obtained by inserting the mutant proviral DNA into the pSV2neo plasmid. Clones with a valine mutation at position 13 or 15 were incapable of transforming cells, while all other mutants with GTP-binding activity were competent. A mutant with a substitution of valine for glycine at position 10 which had lost its ability to bind GTP and its autokinase activity was fully capable of transforming NIH 3T3 cells. These cells grew in soft agar and rapidly formed tumors in nude mice. The p21 of cell lines derived from tumor explants still lacked the autokinase activity. These findings suggest that the glycine-rich consensus sequence is important in controlling p21 activities and that certain mutations may confer to p21 its active conformation without participation of ligand binding.

scholarly journals A tyrosine residue essential for catalytic activity in aminopeptidase A

1997 ◽  
Vol 327 (3) ◽  
pp. 883-889 ◽  
Author(s):  
Gilles VAZEUX ◽  
Xavier ITURRIOZ ◽  
Pierre CORVOL ◽  
Catherine LLORENS-CORTÈS
Keyword(s):  
Catalytic Activity ◽  
Transition State ◽  
Active Site ◽  
Consensus Sequence ◽  
Zinc Ion ◽  
Cysteine Residue ◽  
Enzymic Activity ◽  
Site Directed Mutagenesis ◽  
Tyrosine Residue ◽  
Aminopeptidase A

Aminopeptidase A (EC 3.4.11.7; APA) is a 130 kDa membrane-bound zinc enzyme that contains the consensus sequence HEXXH (residues 385-389) conserved among the zinc metalloprotease family. In this motif, both histidine residues and the glutamic residue were shown to be involved respectively in zinc co-ordination and catalytic activity. Treatment of APA with N-acetylimidazole results in a loss of enzymic activity; this is prevented by the competitive aminopeptidase inhibitor amastatin, suggesting the presence of an important tyrosine, lysine or cysteine residue at the active site of APA. A tyrosine residue was previously proposed to be involved in the enzymic activity of aminopeptidase N. Furthermore sequence alignment of mouse APA with other monozinc aminopeptidases indicates the presence of a conserved tyrosine (Tyr-471 in APA). The functional role of Tyr-471 in APA was investigated by replacing this residue with a phenylalanine (Phe-471) or a histidine (His-471) residue by site-directed mutagenesis. Kinetic studies showed that the Km values of both mutants were similar to that of the wild-type enzyme, whereas kcat values were decreased by three orders of magnitude and corresponded to a variation in free energy of the rate-limiting step by 4.0 and 4.2 kcal/mol (0.96 and 1.00 kJ/mol) for the Phe-471 and His-471 mutants respectively. The mutation did not modify the inhibitory potency of a thiol-containing inhibitor that strongly chelates the active-site zinc ion, whereas that of a putative analogue of the transition state presumed to mimic the reaction intermediate was reduced. Taken together, these results strongly suggest that the Tyr-471 hydroxy group participates in catalysis by stabilizing the transition state complex through interaction with the oxyanion.

scholarly journals Structural significance of the GTP-binding domain of ras p21 studied by site-directed mutagenesis.

1987 ◽  
Vol 7 (9) ◽  
pp. 3092-3097 ◽  
Author(s):  
D J Clanton ◽  
Y Y Lu ◽  
D G Blair ◽  
T Y Shih
Keyword(s):  
Cell Lines ◽  
Consensus Sequence ◽  
Point Mutations ◽  
Soft Agar ◽  
Binding Activity ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Gtp Binding ◽  
Nih 3T3 ◽  
Autokinase Activity

Point mutations of p21 proteins were constructed by oligonucleotide-directed mutagenesis of the v-rasH oncogene, which substituted amino acid residues within the nucleotide-binding consensus sequence, GXG GXGK. When the glycine residue at position 10, 13, or 15 was substituted with valine, the viral rasH product p21 lost its GTP-binding and autokinase activities. Other substitutions at position 33, 51, or 59 did not impair its binding activity. G418-resistant NIH 3T3 cell lines were derived by transfection with constructs obtained by inserting the mutant proviral DNA into the pSV2neo plasmid. Clones with a valine mutation at position 13 or 15 were incapable of transforming cells, while all other mutants with GTP-binding activity were competent. A mutant with a substitution of valine for glycine at position 10 which had lost its ability to bind GTP and its autokinase activity was fully capable of transforming NIH 3T3 cells. These cells grew in soft agar and rapidly formed tumors in nude mice. The p21 of cell lines derived from tumor explants still lacked the autokinase activity. These findings suggest that the glycine-rich consensus sequence is important in controlling p21 activities and that certain mutations may confer to p21 its active conformation without participation of ligand binding.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

scholarly journals Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein

2021 ◽  
Author(s):  
Chen-Long Wang ◽  
Jing-Chi Li ◽  
Ci-Xiang Zhou ◽  
Cheng-Ning Ma ◽  
Di-Fei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Rho Gtpase ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Breast Cancer Cell Lines ◽  
Smad7 Protein

Abstract Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

scholarly journals MiR-326 mediates malignant biological behaviors of lung adenocarcinoma by targeting ZEB1

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110093
Author(s):  
Mingxin Liu ◽  
Hong Wu ◽  
Yiqiang Liu ◽  
Yan Tan ◽  
Songtao Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Invasion And Migration ◽  
Transwell Invasion Assay ◽  
Enhancer Binding Protein ◽  
Adenocarcinoma Cells ◽  
And Migration ◽  
Related Proteins

MiR-326 functions as an antioncogene in the several types of cancer. However, the underling mechanisms through which miRNA-326 regulates the anti-carcinogenesis of lung adenocarcinoma have remained elusive. The aim of this study was to explore the role and regulatory mechanism of miR-326 in cell proliferation, invasion, migration and apoptosis in lung adenocarcinoma. Quantitative real-time PCR (qRT-PCR) was used to detect the expression pattern of miR-326 in human bronchial epithelial cells (HBES-2B), 4 kinds of lung adenocarcinoma cell lines (H23, H1975, H2228, H2085) and 20 lung adenocarcinoma tissues. Then, H23 cells were infected with miR-326 mimics, miR-326 inhibitors and si-ZEB1 to build up-regulated miR-326 cell lines, down-regulated ZEB1(zinc-finger-enhancer binding protein 1)cell lines, simultaneous down-regulated ZEB1 and miR-326 cell lines. Moreover, CCK-8 assay, transwell invasion assay, wound healing assay and flow cytometry assay were employed to examine the effects of miR-326 and ZEB1 on the proliferation, invasion, migration and apoptosis abilities of H23 cells. Western blot was performed to explore the effects of miR-326 and ZEB1 on the expression of invasion and migration related proteins N-cadherin, E-cadherin, MMP7, MMP13, SLUG and apoptotic proteins PARP, BAX. On the mechanism, a dual-luciferase reporter gene was used to measure the target relationship between miR-326 and ZEB1. MiR-326 expression was significantly downregulated in lung adenocarcinoma tissues and cells. Overexpression of miR-326 significantly inhibited the malignant behaviors of H23 cells. Mechanically, luciferase reporter assay showed that ZEB1 was a direct target of miR-326. MiR-326 mimic downregulated the expression of ZEB1. Furthermore, knocking down ZEB1 strongly inhibited the proliferation, invasion and migration of H23 cells but promoted apoptosis. MiR-326 could target ZEB1 to inhibit the proliferation, invasion and migration of lung adenocarcinoma cells and promote apoptosis, which is a potential therapeutic target for lung adenocarcinoma.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

scholarly journals Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals Long non-coding RNA CCDC183-AS1 acts AS a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
He Zhu ◽  
Hongwei Zhang ◽  
Youliang Pei ◽  
Zhibin Liao ◽  
Furong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Human Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Regulatory Relationship

Abstract Background Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1. Results Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC. Conclusions CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.

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