MicroRNA-449a delays lung cancer development through inhibiting KDM3A/HIF-1α axis

Abstract Background It has been established that microRNA (miR)-449a is anti-tumorigenic in cancers, including lung cancer. Therefore, this study further explored miR-449a-mediated mechanism in lung cancer, mainly focusing on lysine demethylase 3A/hypoxia-induced factor-1α (KDM3A/HIF-1α) axis. Methods miR-449a, KDM3A and HIF-1α levels in lung cancer tissues and cell lines (A549, H1299 and H460) were measured. Loss- and gain-of-function assays were performed and then cell proliferation, cell cycle, apoptosis, invasion and migration were traced. The relationship between KDM3A, miR-449a and HIF-1α was verified. Tumor growth in vivo was also monitored. Results Both lung cancer tissues and cells exhibited reduced miR-449a and raised KDM3A and HIF-1α levels. miR-449a interacted with KDM3A; HIF-1α could bind with KDM3A. Up-regulating miR-449a hindered while suppressing miR-449a induced lung cancer development via mediating HIF-1α. Elevating KDM3A promoted cellular aggression while down-regulating KDM3A had the opposite effects. Up-regulating KDM3A or HIF-1α negated up-regulated miR-449a-induced effects on cellular growth in lung cancer. Restoring miR-449a impaired tumorigenesis in vivo in lung cancer. Conclusion It is eventually concluded that miR-449a delays lung cancer development through suppressing KDM3A/HIF-1α axis.

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Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

Cancer Biomarkers ◽

10.3233/cbm-210189 ◽

2021 ◽

pp. 1-9

Author(s):

Huan Guo ◽

Baozhen Zeng ◽

Liqiong Wang ◽

Chunlei Ge ◽

Xianglin Zuo ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Lung Cancer Cells ◽

Invasion And Migration ◽

And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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Impact of protamine I on colon cancer proliferation, invasion, migration, diagnosis and prognosis

Biological Chemistry ◽

10.1515/hsz-2017-0222 ◽

2018 ◽

Vol 399 (3) ◽

pp. 265-275 ◽

Cited By ~ 1

Author(s):

Zhi Chen ◽

Chunyu Shi ◽

Shuohui Gao ◽

Defeng Song ◽

Ye Feng

Keyword(s):

Colon Cancer ◽

Cell Invasion ◽

Cell Apoptosis ◽

Xenograft Model ◽

Enzyme Linked Immunosorbent Assay ◽

Invasion And Migration ◽

Diagnosis And Prognosis ◽

And Migration ◽

Cancer Tissues

AbstractThis paper investigates protamine I (PRM1) expression and its effects on proliferation, invasion and migration of colon cancer cells as well as its function in clinical diagnosis and prognosis. Gene chips were used to screen differentially expressed genes. PRM1 expression was detected by Western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). Hematoxylin and eosin (HE) staining and immunohistochemistry were utilized to compare the expression of PRM1 from multiple differentiation levels of colon cancer tissues. Cell viability, cell apoptosis and cell cycle were tested using the MTT assay and flow cytometry. Cell invasion and migration capability were tested using the Transwell assay and wound healing.In vivoeffects of PRM1 on colon cancer were explored using a xenograft model.PRM1expression in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expression level of PRM1 was significantly higher in colon cancer tissues and the staining degree of PRM1 in poorly-differentiated was stronger. pcDNA3.1-PRM1 decreased cell apoptosis while it increased the proliferation, cell invasion and migration. The si-PRM1 group displayed an opposite tendency. The serum PRM1 level was significantly higher and could serve as a diagnostic biomarker for colon cancer.

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Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4

AJP Cell Physiology ◽

10.1152/ajpcell.00262.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. C903-C912 ◽

Cited By ~ 3

Author(s):

Shuai Wu ◽

Han Chen ◽

Ling Zuo ◽

Hai Jiang ◽

Hongtao Yan

Keyword(s):

Cell Cycle ◽

Uveal Melanoma ◽

Noncoding Rna ◽

Cell Cycle Progression ◽

Melanoma Cells ◽

Cell Cycle Distribution ◽

Invasion And Migration ◽

And Migration

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

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lncRNA OXCT1-AS1 Promotes Metastasis in Non-Small-Cell Lung Cancer by Stabilizing LEF1, In Vitro and In Vivo

BioMed Research International ◽

10.1155/2021/4959381 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Binru Li ◽

Libo Zhu ◽

Linlin Li ◽

Rui Ma

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Small Cell ◽

Small Cell Lung ◽

Invasion And Migration ◽

And Migration

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.

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MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3

Frontiers in Oncology ◽

10.3389/fonc.2021.688882 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yibin Zhao ◽

Hongyi Zhou ◽

Jie Shen ◽

Shaohui Yang ◽

Ke Deng ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Qrt Pcr ◽

And Migration ◽

Cancer Tissues

BackgroundDysregulated microRNAs (miRNAs) are common in human cancer and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, this study aimed to evaluate the expression and biological function of miR-1236-3p in colon cancer.MethodsThis study screened the miRNA in normal and colon cancer tissues through array analysis. In addition, quantitative Reverse Transcription–Polymerase Chain Reaction (qRT-PCR) analysis was performed to validate the expression of miR-1236-3p in normal and tumor tissues from colon cancer patients and cancer cell lines. Online predicting algorithms and luciferase reporter assays were also employed to confirm Doublecortin Like Kinase 3 (DCLK3) was the target for miR-1236-3p. Moreover, the impact of miR-1236-3p on the progression of colon cancer was evaluated in vitro and in vivo. Western blotting and qRT-PCR were also performed to investigate the interactions between miR-1236-3p and DCLK3.ResultsMiR-1236-3p was significantly downregulated in colon cancer tissues and its expression was associated with the TNM stage and metastasis of colon. In addition, the in vitro and in vivo experiments showed that miR-1236-3p significantly promoted cancer cell apoptosis and inhibited the proliferation, invasion, and migration of cancer cells. The results also showed that miR-1236-3p hindered Epithelial–mesenchymal Transition (EMT) by targeting DCLK3. Moreover, the expression of DCLK3 mediated the effects of miR-1236-3p on the progression of cancer.ConclusionsMiR-1236-3p functions as a tumor suppressor in colon cancer by targeting DCLK3 and is therefore a promising therapeutic target for colon cancer.

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Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205778 ◽

2019 ◽

Vol 73 (3) ◽

pp. 139-146

Author(s):

Hao-Ran Li ◽

Bai-Quan Qiu ◽

Jian Gao ◽

Chun Jin ◽

Jia-Hao Jiang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Western Blot ◽

Blot Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Invasion And Migration ◽

And Migration ◽

The Relationship

AimsTo unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC.MethodsImmunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods.ResultsElevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate.ConclusionsOur study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.

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CD142 plays a key role in the carcinogenesis of gastric adenocarcinoma by inhibiting BCL2-dependent autophagy

Biochemistry and Cell Biology ◽

10.1139/bcb-2021-0144 ◽

2021 ◽

Author(s):

Weifeng Xu ◽

Beibei Chen ◽

Dianshan Ke ◽

Xiaobing Chen

Keyword(s):

Cell Death ◽

Malignant Tumors ◽

Xenograft Tumor ◽

Invasion And Migration ◽

Autophagic Degradation ◽

In Vivo Analysis ◽

And Migration ◽

Cancer Tissues

CD142 is expressed on the surface of multiple malignant tumors and contributes to various carcinogenesis. However, the role of CD142 in the pathogenesis of GAC remains unclear. This study aimed to investigate the role of CD142 in GAC carcinogenesis. Our results showed that CD142 expression was significantly increased in GAC cancer tissues, especially in those with significant invasion or metastasis. The invasion and migration of CD142-positive SNU16 cells were significantly increased compared with those of CD142-negative cells. Moreover, CD142 overexpression promoted the invasion and migration of SGC083 cells, but CD142 silencing was contrary. In addition, there was a positive correlation between CD142 expression of cancer tissues and serum IL-8 levels. CD142 overexpression promotes IL-8 production in SGC083 cells. In vivo analysis showed that the implantation of CD142-positive SNU16 cells promoted the growth of xenograft tumor and the production of IL-8. Mechanistically, CD142 silencing not only inhibited the expression of BCL2 and the interaction between BCL2 and Beclin1, but also promoted the autophagic response in SGC083. Furthermore, CD142 silencing-induced IL-8 degradation was recovered by treatment of autophagy inhibitor 3-MA. CD142 can inhibit autophagic cell death and the autophagic degradation of IL-8 in GAC, which exerts an effective effect on GAC carcinogenesis.

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Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924

Cell Death and Disease ◽

10.1038/s41419-019-2123-y ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 11

Author(s):

Shutao Pan ◽

Ming Shen ◽

Min Zhou ◽

Xiuhui Shi ◽

Ruizhi He ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Proliferation ◽

Cell Invasion ◽

Molecular Mechanisms ◽

Invasion And Migration ◽

Cancer Aggressiveness ◽

And Migration

AbstractDysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.

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ZNF280A Promotes Lung Adenocarcinoma Development through Regulating the Expression of EIF3C

10.21203/rs.3.rs-26101/v1 ◽

2020 ◽

Author(s):

Hongsheng Liu ◽

Yingzhi Qin ◽

Na Zhou ◽

Dongjie Ma ◽

Yingyi Wang

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Small Cell Lung ◽

Normal Tissues ◽

Tumor Promotor ◽

And Migration ◽

First Time ◽

The Relationship

Abstract Background: Lung cancer is the most commonly diagnosed malignant tumor worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer (NSCLC). The relationship between ZNF280A and LUAD has not been demonstrated and remains unclear. Methods: In this study, it was demonstrated that ZNF280A was upregulated in LUAD tissues compared with the normal tissues. Further investigations indicated that the overexpression/knockdown of ZNF280A could promote/inhibit proliferation, colony formation and migration of LUAD cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of ZNF280A could also suppress tumorigenicity of LUAD cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of ZNF280A and identified EIF3C as the potential target. Results: Furthermore, our study revealed that knockdown of EIF3C could inhibit development of LUAD in vitro, and alleviate the ZNF280A overexpression induced promotion of LUAD. Conclusions: In conclusion, our study showed, as the first time, ZNF280A as a tumor promotor for LUAD, whose function was carried out probably through the regulation of EIF3C.

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Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/6646077 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Lili Mao ◽

Xu Ling ◽

Ji Chen

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Poor Prognosis ◽

Clinical Proteomics ◽

Invasion And Migration ◽

Lung Cancer Patients ◽

Qrt Pcr ◽

And Migration ◽

Cancer Tissues

Introduction. Studies have previously shown that Cyclin H (CCNH) is involved in the tumorigenesis and development of many cancers. The increasing research in CCNH is associated with the poor prognosis of most human cancers. Early diagnosis and clinical treatment are still the main challenges for lung cancer treatment. However, the exact role of CCNH in the tumorigenesis of lung cancer remains unclear. Methods. The Tumor Genome Atlas (TCGA) database and the Clinical Proteomics Tumor Analysis Association (CPTAC) database were analyzed to detect key genes that might play an important role in lung cancer. The biological functions of CCNH were further revealed through bioinformatics experiments. The Kaplan-Meier method was applied to explore the relationship between CCNH expression and prognosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression levels of CCNH in 6 lung cancer tissues and 3 cancer cell lines. The effect of CCNH expression on lung cancer progression was studied by in vitro functional experiments. Results. Database analysis screened out candidate oncogenes, and CCNH was of great significance to the tumorigenesis of lung cancer. The higher the expression of CCNH was, the lower the survival rate of lung cancer patients were. The qRT-PCR data illustrated that the CCNH expression level was largely increased in lung cancer tissues and cells. The reduction of CCNH inhibited cell proliferation, invasion, and migration. Conclusion. CCNH was related to poor prognosis, suggesting that CCNH regulated the tumorigenesis and development of lung cancer. Our study suggested that CCNH was a promising biomarker and target in the treatment of lung cancer.

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