scholarly journals Hypoxia-induced HMMR Promotes Cell Proliferation, Migration and Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Duan Lin can ◽  
Jiang Xiu lin ◽  
Tan Lin ◽  
Yuan Yi xiao ◽  
Wang Juan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Related Gene ◽  
Cell Growth And Migration ◽  
Immune Infiltration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract BackgroundHyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the relationships between HMMR and prognosis and tumor-infiltrating lymphocytes in lung adenocarcinoma remain unclear.MethodsHMMR expression was analyzed emoloyed the TIMER, GEPIA, UALCAN, CCLE databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases, the gene mutation of HMMR was analysis by the cBioportal and COSMIC databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.ResultsIn this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene, for instance, CD279, CD274, CTLA4, LAG3, PDCD1LG2, TIGIT and HAVCR2. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. Overall, this study emphasized the significance of HMMR in cancer progression and Immune infiltration of LUAD.ConclusionsWe demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.

scholarly journals Hypoxia Induced HMMR Promotes the NSCLC Progression

2021 ◽  
Author(s):  
Duan Lin can ◽  
Jiang Xiu lin ◽  
Tan Lin ◽  
Yuan Yi xiao ◽  
Wang Juan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Poor Prognosis ◽  
High Expression ◽  
Related Gene ◽  
Cell Growth And Migration ◽  
Immune Infiltration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Hyaluronan mediated motility receptor (also known as RHAMM) is another one of few defined hyaluronan receptors, play pivotal roles in cell growth. However, the functionof HMMR in lung adenocarcinoma remain unclear.Methods: HMMR expression was analyzed emoloyed the public databases, the prognosis of HMMR was analysis by prognoscan, KMplot and GEPIA databases. The GO and KEGG pathway was analysis by the DAVID and GSEA software. The correlation between the HMMR expression was analysis by the TIMER databases, the gene and protein networks was analysis by Genemania and STRING databases, the DNA methylation was analysis by the MethSurv and UALCAN databases. The expression of HMMR was analysis by IHC and qPCR, the function of HMMR on cell proliferation and migration was examine by the cell growth curve, clone information, transwell and wound healing assay.Results: in this study, we find that HMMR was elevated in LUAD and it’s highly expression associated with the poor prognosis and lymph node metastasis. Furthermore, the expression of HMMR was induced by hypoxia in LUAD. HMMR expression level not only positively correlation with the different immune cells, but also positively correlation with the expression of immune checkpoints related gene. Finally, depletion of HMMR significantly represses the cell growth and migration of NSCLC. We also found that the HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in NSCLC, depletion of TMPO-AS1 and over-expression the Let-7b-5p would result in decreased the expression of HMMR in NSCLC cells, the TMPO-AS1 was positively with the HMMR and negatively related to the Let-7b-5p in NSCLC. Overall, this study emphasized the significance of HOXB7/TMPO-AS1/Let-7b-5p axis mediated high expression of HMMR in cancer progression and Immune infiltration of LUAD.Conclusions: we demonstrated HMMR was elevated in LUAD and positively relation to poor prognosis. We find the hypoxia microenvironment and DNA hypomethylation able to up-regulation of the HMMR expression. Additionally, HMMR expression was positive with the diverse immune cell and immune regulator related gene in LUAD. Finally, we found that depletion of HMMR was inhibits the cell proliferation and migration ability of NSCLC cells. These findings suggest that HMMR could be served as a biomarker for prognosis and immune infiltration in LUAD.

scholarly journals SKA3 up-regulation promotes lung adenocarcinoma growth and is a predictor of poor prognosis

2019 ◽  
Vol 14 (1) ◽  
pp. 392-399
Author(s):  
Rong-Li Sun ◽  
Feng-Juan Liu ◽  
Xiao Wu ◽  
Li-Sheng Wang ◽  
Peng-Fei Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Western Blot ◽  
Lung Adenocarcinoma ◽  
A549 Cell ◽  
Poor Prognosis ◽  
A549 Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

AbstractObjectiveThe objective of this research is to investigate the expression and function of SKA3 in lung adenocarcinoma.MethodsThe mRNA expression level of SKA3 in lung adenocarcinoma and its association with clinic-pathological factors were analyzed using data obtained from the TCGA database. Small interfering RNA (siRNA) for SKA3 (si-SKA3) was used to down-regulate SKA3 in A549 cells. pcDNA3.1- SKA3 was used to overexpress SKA3 in A549 cells. The proliferation ability of A549 cells was determined via MTT assay and colony formation assay. A wound healing assay was performed to examine the migration ability of A549 cells. The protein expression of p-MEK, MEK, p-ERK and ERK were determined by western blot.ResultsWe found that SKA3 is up-regulated in lung adenocarcinoma compared to the normal lung tissues. Kaplan-Meier analysis showed that high SKA3 expression is markedly associated with poor prognosis in lung adenocarcinoma patients. SKA3 expression is significantly correlated with age, gender, pathologic-stage, pathologic-N and pathologic-M. Moreover, depleting SKA3 obviously inhibited A549 cell proliferation and migration in vitro, while overexpression of SKA3 notably increased A549 cell proliferation and migration. Western blot analysis showed that the protein expression ratio of p-MEK/MEK and p-ERK/ERK decreased noticeably after depleting SKA3.ConclusionSKA3 expression was enhanced and associated with poor prognosis in lung adenocarcinoma patients, and it might play a facilitating role in cell growth and motility by regulating the MAPK signaling pathway.

scholarly journals LINC01089 suppresses lung adenocarcinoma cell proliferation and migration via miR-301b-3p/STARD13 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Qian ◽  
Yan Zhang ◽  
Haoming Ji ◽  
Yucheng Shen ◽  
Liangfeng Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
High Morbidity ◽  
Lipid Transfer ◽  
Protein Coding ◽  
Cell Proliferation And Migration ◽  
Reduce Cell Proliferation ◽  
And Migration ◽  
Insight Into ◽  
Proliferation And Migration

Abstract Background Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD. Methods The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student’s t test or one-way analysis of variance. Results LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells. Conclusion LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.

scholarly journals Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3046
Author(s):  
Ming-Huei Chou ◽  
Hui-Ching Chuang ◽  
Yu-Tsai Lin ◽  
Ming-Hsien Tsai ◽  
Ying-Hsien Kao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Xenograft Model ◽  
Mtor Inhibitors ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hnscc Cell ◽  
Proliferation And Migration

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

scholarly journals Down-regulated LncR-MALAT1 suppressed cell proliferation and migration by inactivating autophagy in bladder cancer

RSC Advances ◽  
2018 ◽  
Vol 8 (54) ◽  
pp. 31019-31027
Author(s):  
Jiude Qi ◽  
Yanfeng Chu ◽  
Guangyan Zhang ◽  
Hongjun Li ◽  
Dongdong Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Cell Proliferation And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Proliferation And Migration

Long non-coding RNA-metastasis-associated lung adenocarcinoma transcript (LncR-MALAT) is highly expressed in a variety of tumors, which can affect the progression of tumor cells.

scholarly journals Over-expression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin

2020 ◽  
Author(s):  
Jianwei Zhang ◽  
Zhongmin Lan ◽  
Guotong Qiu ◽  
Hu Ren ◽  
Yajie Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cell Cycle Progression ◽  
Over Expression ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Abstract Background: Pancreatic cancer is a malignant tumor with high mortality. Acidic nuclear phosphoprotein 32 family member E (ANP32E), a specific H2A.Z chaperone, has been shown to contribute to breast cancer development. However, the significance of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the role of ANP32E in pancreatic cancer. Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and the correlation between ANP32E expression and patients’ survival were analyzed from the TCGA database. ANP32E was over-expressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle and transwell experiments were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression. Results: ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor prognosis in pancreatic cancer patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E over-expression promoted the proliferation and migration of both cells. In addition, ANP32E accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells. Conclusion: Our results propose that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

scholarly journals TIFA Promotes Cell Survival and Migration in Lung Adenocarcinoma

2018 ◽  
Vol 47 (5) ◽  
pp. 2097-2108 ◽  
Author(s):  
Wanfu Men ◽  
Wenya Li ◽  
Jungang Zhao ◽  
Yu Li
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cancer Cell ◽  
Lung Cancer Cell ◽  
Cycle Arrest ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: TNF-α receptor-associated factor (TRAF)-interacting protein with a forkhead-associated (FHA) domain (TIFA) may mediate the impact of TRAF on the development of lung cancer. The current study was conducted to investigate the expression of TIFA in lung adenocarcinoma and its potential role in the regulation of cancer cell proliferation and migration, and its influence on patient survival. Methods: Specimens of lung adenocarcinoma tissues and their adjacent normal lung tissues were obtained from 116 patients who underwent surgical resection of lung cancer. The expression of TIFA in the lung tissues was examined by immunohistochemistry, immunoblotting, and real-time RT-PCR in four different lung cancer cell lines and one normal bronchial epithelial cell line (BEAS-2B). TIFA was silenced by RNAi technique, and cell proliferation was then assessed by the CCK8 method. Furthermore, cell migration was determined by wound-healing trans-well and wound-healing migration assays. Additionally, cell-cycle arrest and apoptosis were assessed by flow cytometry analysis. Results: TIFA was positively detected in 63 (54.3%) out of 116 lung adenocarcinoma specimens, which was significantly higher than the respective rate established in normal tissues adjacent to the tumor (30.1%, p < 0.05). The overall survival rate was significantly lower in the patients with positive TIFA expression than that in the patients with negative TIFA expression (p < 0.05). TIFA was also highly expressed in the lung cancer cell lines (H1299, H1975, and HCC827) tested. It is noteworthy that siRNA suppressed the expression of TIFA, which contributed to the attenuation of cell proliferation and migration, but promoted cell-cycle arrest and apoptosis. Furthermore, the silencing of TIFA caused upregulation of p53, p21, and cleaved-caspase-3, but downregulation of Bcl-2, cyclin D1, and CDK4, as well as phosphorylation of IKKß, IκB, and p65. Conclusions: TIFA may serve as a biomarker in the prediction of lung adenocarcinoma. Furthermore, TIFA may modulate lung cancer cell survival and proliferation through regulating the synthesis of apoptosis-associated proteins.

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