SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

AbstractThe protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.

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Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

Discover Oncology ◽

10.1007/s12672-021-00415-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zehua Zhang ◽

Fei Dai ◽

Fei Luo ◽

Wenjie Wu ◽

Shuai Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Therapy ◽

Disease Free Survival ◽

Tumor Stage ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Proliferation And Metastasis ◽

New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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ALCAP2 inhibits lung adenocarcinoma cell proliferation, migration and invasion via the ubiquitination of β-catenin by upregulating the E3 ligase NEDD4L

Cell Death and Disease ◽

10.1038/s41419-021-04043-6 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Weijie Zhang ◽

Ruochen Zhang ◽

Yuanyuan Zeng ◽

Yue Li ◽

Yikun Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Nuclear Translocation ◽

E3 Ligase ◽

Migration And Invasion ◽

Drug Candidate ◽

Proliferation And Metastasis

AbstractLung cancer is recognized as the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the predominant subtype, accounting for approximately 85% of lung cancer cases. Although great efforts have been made to treat lung cancer, no proven method has been found thus far. Considering β, β-dimethyl-acryl-alkannin (ALCAP2), a natural small-molecule compound isolated from the root of Lithospermum erythrorhizon. We found that lung adenocarcinoma (LUAD) cell proliferation and metastasis can be significantly inhibited after treatment with ALCAP2 in vitro, as it can induce cell apoptosis and arrest the cell cycle. ALCAP2 also significantly suppressed the volume of tumours in mice without inducing obvious toxicity in vivo. Mechanistically, we revealed that ALCAP2-treated cells can suppress the nuclear translocation of β-catenin by upregulating the E3 ligase NEDD4L, facilitating the binding of ubiquitin to β-catenin and eventually affecting the wnt-triggered transcription of genes such as survivin, cyclin D1, and MMP9. As a result, our findings suggest that targeting the oncogene β-catenin with ALCAP2 can inhibit the proliferation and metastasis of LUAD cells, and therefore, ALCAP2 may be a new drug candidate for use in LUAD therapeutics.

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LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1

Cancer Cell International ◽

10.1186/s12935-021-02253-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ru-nan Zhang ◽

Dong-mei Wu ◽

Li-ping Wu ◽

Guo-wei Gao

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gear Up ◽

Underlying Mechanisms

Abstract Background Emerging studies have shown that long noncoding RNAs (lncRNAs) predominantly function in the carcinogenesis of multiple developing human tumors. The current study aimed to investigate the underlying mechanisms of LINC00337 in lung adenocarcinoma. Methods We analyzed TCGA and GTEx datasets and chose LINC00337 as the research object. Cell proliferation, cell apoptosis, cell cycle, migration, and invasion were detected in the gain and loss experiments of LINC00337 both in vitro and in vivo. Moreover, RNA pull-down, luciferase reporter assays, western blotting analysis, and rescue experiments were performed to investigate the underlying molecular mechanisms of LINC00337 function. Results LINC00337 expression was remarkably upregulated in lung adenocarcinoma. In addition, LINC00337 knockdown was shown to repress cell migration, invasion, and proliferation, as well as the cell cycle, and gear up apoptosis in lung adenocarcinoma in vitro and in vivo. With respect to the mechanism, LINC00337 knockdown boosted miR-1285-3p expression and then restrained YTHDF1 expression post-transcriptionally. Crucially, both miR-1285-3p decrement and YTHDF1 overexpression successfully reversed the influence on cell proliferation, migration, invasion, and apoptosis caused by LINC00337 shRNA. Conclusions These results suggest that LINC00337 acts as an oncogenic lncRNA, targeting miR-1285-3p and regulating YTHDF1 expression, to promote the progression of lung adenocarcinoma.

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Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC

Cell Death and Disease ◽

10.1038/s41419-021-03990-4 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Hanyue Chang ◽

Qiaoshi Xu ◽

Jiayi Li ◽

Mingyu Li ◽

Zhiyuan Zhang ◽

...

Keyword(s):

Critical Role ◽

Lactate Production ◽

Metabolic Reprogramming ◽

Migration And Invasion ◽

Histone Deacetylase 3 ◽

Proliferation And Metastasis ◽

Immunosuppressive Microenvironment ◽

Transcriptional Complex

AbstractPyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. The biological functions of PKM2 were investigated in vitro and in vivo. Lactate production and the expression of Galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. The mechanism of lactate regulating Galectin-9 expression through NF-κB signaling was explored in vitro. Overexpression of PKM2 correlates with poor prognosis in HNSCC patients. Silencing PKM2 markedly inhibits proliferation and metastasis capacity in vivo and in vitro, and vice versa. The glycolysis and glycolytic capacity are significantly decreased after PKM2 silencing. Lactate secretion induced by PKM2 significantly promotes migration and invasion capacity. Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.

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Circular RNA CDR1as Inhibits the Metastasis of Gastric Cancer through Targeting miR-876-5p/GNG7 Axis

Gastroenterology Research and Practice ◽

10.1155/2021/5583029 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiajia Jiang ◽

Rong Li ◽

Junyi Wang ◽

Jie Hou ◽

Hui Qian ◽

...

Keyword(s):

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Luciferase Reporter Gene ◽

Mesenchymal Transition ◽

Underlying Mechanisms

Circular RNA CDR1as has been demonstrated to participate in various cancer progressions as miRNA sponges. The exact underlying mechanisms of CDR1as on gastric cancer (GC) metastasis remain unknown. Here, we found that CDR1as knockdown facilitated GC cell migration and invasion while its overexpression inhibited the migration and invasion abilities of GC cells in vitro and in vivo. Moreover, epithelial-mesenchymal transition- (EMT-) associated proteins and MMP2 and MMP9 were downregulated by CDR1as. Bioinformatics analysis combined with dual-luciferase reporter gene assays, western blot, RT-qPCR analysis, and functional rescue experiments demonstrated that CDR1as served as a miR-876-5p sponge and upregulated the target gene GNG7 expression to suppress GC metastasis. In summary, our findings indicate that CDR1as suppresses GC metastasis through the CDR1as/miR-876-5p/GNG7 axis.

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KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion

BioMed Research International ◽

10.1155/2021/8249293 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Jing Chen ◽

Cui-Cui Zhao ◽

Fei-Ran Chen ◽

Guo-Wei Feng ◽

Fei Luo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Pancreatic Ductal Adenocarcinoma ◽

Disease Free Survival ◽

High Expression ◽

Ductal Adenocarcinoma ◽

Migration And Invasion

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

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Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo

Disease Markers ◽

10.1155/2019/6383685 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Fu-Tao Chen ◽

Fu-Kuan Zhong

Keyword(s):

Tumor Growth ◽

Lung Adenocarcinoma ◽

Clinical Stage ◽

Migration And Invasion ◽

Expression Levels ◽

Adenocarcinoma Cells ◽

Lung Adenocarcinoma Cells ◽

Tumor Growth And Metastasis

Objective. To determine the expression levels of KIF18A in lung adenocarcinoma and its relationship with the clinicopathologic features of patients undergoing radical colectomy and explore the potential role in the progression of lung adenocarcinoma. Methods. Immunohistochemical assays were performed to explore the expression levels of KIF18A in 82 samples of lung adenocarcinoma and corresponding normal tissues. According to the levels of KIF18A expression in lung adenocarcinoma tissue samples, patients were classified into the KIF18A high expression group and low expression group. Clinical data related to the perioperative clinical features (age, gender, smoking, tumor size, differentiation, clinical stage, and lymph node metastasis), the potential correlation between KIF18A expression levels, and clinical features were analyzed, and the effects of KIF18A on lung adenocarcinoma cell proliferation, migration, and invasion were measured by colony formation assay, MTT assay, wound healing assay, and transwell assays. The possible effects of KIF18A on tumor growth and metastasis were measured in mice through tumor growth and tumor metastasis assays in vivo. Results. KIF18A in lung adenocarcinoma tissues. Further, KIF18A was significantly associated to clinical characteristic features including the tumor size (P=0.033) and clinical stage (P=0.041) of patients with lung adenocarcinoma. Our data also investigated that KIF18A depletion dramatically impairs the proliferation, migration, and invasion capacity of lung adenocarcinoma cells in vitro and inhibits tumor growth and metastasis in mice. Conclusions. Our study reveals the involvement of KIF18A in the progression and metastasis of lung adenocarcinoma and provides a novel therapeutic target for the treatment of lung adenocarcinoma.

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circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

Molecular Cancer ◽

10.1186/s12943-019-1081-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 15

Author(s):

Sen Wang ◽

Dong Tang ◽

Wei Wang ◽

Yining Yang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Gastric Cancer ◽

Bioinformatic Analysis ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Tumour Metastasis ◽

Genome Wide ◽

Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

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The TWIST1-centered competing endogenous RNA network promotes proliferation, invasion, and migration of lung adenocarcinoma

Oncogenesis ◽

10.1038/s41389-019-0167-6 ◽

2019 ◽

Vol 8 (11) ◽

Cited By ~ 4

Author(s):

Wenjie Xia ◽

Qixing Mao ◽

Bing Chen ◽

Lin Wang ◽

Weidong Ma ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Migration And Invasion ◽

Circular Rnas ◽

Messenger Rnas ◽

Competing Endogenous Rna ◽

Invasion And Migration ◽

Non Coding Rnas ◽

And Migration

Abstract The proposed competing endogenous RNA (ceRNA) mechanism suggested that diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs could communicate with each other by competing for binding to shared microRNAs. The ceRNA network (ceRNET) is involved in tumor progression and has become a hot research topic in recent years. To date, more attention has been paid to the role of non-coding RNAs in ceRNA crosstalk. However, coding transcripts are more abundant and powerful than non-coding RNAs and make up the majority of miRNA targets. In this study, we constructed a mRNA-mRNA related ceRNET of lung adenocarcinoma (LUAD) and identified the highlighted TWIST1-centered ceRNET, which recruits SLC12A5 and ZFHX4 as its ceRNAs. We found that TWIST1/SLC12A5/ZFHX4 are all upregulated in LUAD and are associated with poorer prognosis. SLC12A5 and ZFHX4 facilitated proliferation, migration, and invasion in vivo and in vitro, and their effects were reversed by miR-194–3p and miR-514a-3p, respectively. We further verified that SLC12A5 and ZFHX4 affected the function of TWIST1 by acting as ceRNAs. In summary, we constructed a mRNA-mRNA related ceRNET for LUAD and highlighted the well-known oncogene TWIST1. Then we verified that SLC12A5 and ZFHX4 exert their oncogenic function by regulating TWIST1 expression through a ceRNA mechanism.

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LncRNA DQ786243 contributes to proliferation and metastasis of colorectal cancer both in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20160048 ◽

2016 ◽

Vol 36 (3) ◽

Cited By ~ 16

Author(s):

Longci Sun ◽

Hanbing Xue ◽

Chunhui Jiang ◽

Hong Zhou ◽

Lei Gu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Proliferation And Metastasis ◽

Non Coding Rnas ◽

Colorectal Cancer Progression

This article aims to find the key long non-coding RNAs (LncRNAs) associated with colorectal cancer (CRC) and to study its biological functions in colorectal cancer progression. Our study has shown that upregulated LncRNA DQ786243 can regulate cell proliferation, cell cycle progression, cell apoptosis, migration, and invasion in CRC cells. Xenograft experiments confirmed that the growth of xenograft tumors formed by CRC cells was suppressed after silencing LncRNA DQ786243 expression. In conclusion, our study suggests that LncRNA DQ786243 is an oncogene that promotes tumor progression and leads us to propose that LncRNAs may serve as key regulatory hubs in CRC progression.

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