scholarly journals MicroRNA-892a regulates laryngocarcinoma cell proliferation via Dicer

2020 ◽  
Vol 245 (14) ◽  
pp. 1222-1232
Author(s):  
Jinhui Dong ◽  
Jianxing Wang ◽  
Chunguang Shan ◽  
Haizhong Zhang ◽  
Ou Xu
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Laryngeal Cancer ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Epithelial Cell Line ◽  
Dicer Expression

MicroRNA (miR) plays a critical role in the progression of multiple malignancies. Nevertheless, knowledge of the role it plays in laryngeal cancer is limited. In this study, we explored the role of miR-892a in laryngeal cancer cell proliferation and apoptosis. miR-892a expression was increased in 17 laryngeal cancer samples and cells compared with that in healthy tissues, laryngeal cancer normal surrounding tissues, and the NP69 human nasopharyngeal epithelial cell line. Conversely, Dicer expression was downregulated in human laryngeal cancer samples as well as in the laryngeal cancer cell lines. CCK-8 assays and colony formation assay confirmed that depleted miR-892a expression damaged the proliferation and growth of TU212 and M4E cells. Annexin V/PI flow cytometry displayed that miR-892a inhibition led to increased apoptosis of TU212 and M4E cells. By conducting bioinformatic analysis and dual-luciferase reporter assay, it was revealed that that miR-892a targets Dicer 3′-UTR for silencing. Dicer expression inhibition offsets the effect of miR-892a on the growth and apoptosis of laryngeal cancer cells. Dicer overexpression displayed similar phenotype with miR-892a inhibition on the properties of laryngeal cancer cells. Results of in vivo experiments further confirmed that miR-892a silencing suppressed tumor growth in a mouse model. Hence, the results of this study provide new ideas about the biological and molecular mechanisms behind laryngeal cancer progression, thereby obtaining novel laryngeal cancer treatments. Impact statement This work expanded the knowledge of the molecular mechanisms underlying LC progression by exploring the role of miR-892a in the viability of TU212 and M4E cells. The results showed that miR-892a, which exhibited elevated expression in LC cells and tissue specimens of patients with LC, exerted an inhibitory effect on Dicer expression, whereas silencing of miR-892a in TU212 and M4E cells hindered cell proliferation and growth and promoted apoptosis. Furthermore, miR-892a was demonstrated to directly target Dicer 3′-UTR and inhibit its expression. These findings demonstrated that miR-892a acted as an LC oncogene via its action on Dicer, which further confirmed that miR-892a can serve as a diagnostic indicator or promising agent for LC treatment.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

2021 ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

Development of a novel method for the bioanalysis of benfotiamine and sulbutiamine in cancer cells

2016 ◽  
Vol 8 (28) ◽  
pp. 5596-5603 ◽  
Author(s):  
Jaeah Kim ◽  
Christopher P. Hopper ◽  
Kelsey H. Connell ◽  
Parisa Darkhal ◽  
Jason A. Zastre ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Biological Samples ◽  
Cancer Cell Proliferation ◽  
Essential Step ◽  
Novel Method

Quantification of benfotiamine and sulbutiamine, synthetic thiamine analogs, in biological samples is an essential step toward understanding the role of these thiamine analogs on cancer cell proliferation.

scholarly journals USP46 inhibits cell proliferation in lung cancer through PHLPP1/AKT pathway

2020 ◽  
Author(s):  
Wei Wang ◽  
Meng Chen ◽  
Hailing Xu ◽  
Dongqing Lv ◽  
Suna Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Knock Down

Abstract Background: USP46 has been shown to function as tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers remains unknown. This study was aimed to investigate the role of USP46 in lung cancer tumorigenesis, and to identify the underlying mechanism. Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western Blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from lung cancer patients. The functional role of USP46 in regulating proliferation in lung cancer cells were examined by cell proliferation assay, radiation assay, genetic overexpression and knock down and chemical inhibition of relevant genes. The underlying mechanisms were investigated in multiple lung cancer cell line models by co-immunoprecipitation and ubiquitination assays. Results: This study identified strong downregulation of USP46 and PHLPP1 expression in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under normal growth conditions and during radiation induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. The effect of USP46 knock down on lung cancer cell proliferation was significantly reversed by exposure to radiation and AKT inhibition. Conclusions: USP46 is down-regulated in lung cancer, and it suppresses proliferation of lung cancer cells by inhibiting PHLPP1/AKT pathway. AKT inhibition slows proliferation of USP46 down-regulated lung cancer cells exposed to radiation suggesting a potential therapeutic avenue for USP46 down-regulated lung cancer through a combination of radiation and AKT inhibitor treatment.

scholarly journals The C-Terminus Tail Regulates ERK3 Kinase Activity and Its Ability in Promoting Cancer Cell Migration and Invasion

2020 ◽  
Vol 21 (11) ◽  
pp. 4044 ◽  
Author(s):  
Lobna Elkhadragy ◽  
Hadel Alsaran ◽  
Weiwen Long
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion ◽  
C Terminus

Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein kinase (MAPK) family. It harbors a kinase domain in the N-terminus and a long C-terminus extension. The C-terminus extension comprises a conserved in ERK3 and ERK4 (C34) region and a unique C-terminus tail, which was shown to be required for the interaction of ERK3 with the cytoskeletal protein septin 7. Recent studies have elucidated the role of ERK3 signaling in promoting the motility and invasiveness of cancer cells. However, little is known about the intramolecular regulation of the enzymatic activity and cellular functions of ERK3. In this study, we investigated the role of the elongated C-terminus extension in regulating ERK3 kinase activity and its ability to promote cancer cell migration and invasion. Our study revealed that the deletion of the C-terminus tail greatly diminishes the ability of ERK3 to promote the migration and invasion of lung cancer cells. We identified two molecular mechanisms underlying this effect. Firstly, the deletion of the C-terminus tail decreases the kinase activity of ERK3 towards substrates, including the oncogenic protein steroid receptor co-activator 3 (SRC-3), an important downstream target for ERK3 signaling in cancer. Secondly, in line with the previous finding that the C-terminus tail mediates the interaction of ERK3 with septin 7, we found that the depletion of septin 7 abolished the ability of ERK3 to promote migration, indicating that septin 7 acts as a downstream effector for ERK3-induced cancer cell migration. Taken together, the findings of this study advance our understanding of the molecular regulation of ERK3 signaling by unraveling the role of the C-terminus tail in regulating ERK3 kinase activity and functions in cancer cells. These findings provide useful insights for the development of therapeutic agents targeting ERK3 signaling in cancer.

miR-1825 Accelerates Cell Proliferation and Inhibits Cell Apoptosis of Prostate Cancer via Targeting Suppressor of Cancer Cell Invasion

2021 ◽  
Vol 11 (5) ◽  
pp. 820-831
Author(s):  
Jun-Chao Bai ◽  
Guang-Yi Huang
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Cancer Cell Invasion ◽  
Normal Prostate

Prostate cancer (PC) is one major carcinoma threat to the health of males. microRNAs (miRNAs) are short non-coding transcripts with about 23 nt in length. Booming evidence has verified the various roles of miRNAs in human tumors. miR-1825 was once demonstrated to be highly expressed in PC, but the potential role of miR-1825 in PC has never been clarified yet. This work aimed to explore the function of miR-1825 and reveal the underlying modulation mechanism in PC. First, miR-1825 was detected to be elevated in PC cells compared with normal prostate cells, as proved by RT-qPCR. After miR-1825 expression was inhibited, cell proliferation was hindered and cell apoptosis was promoted, which was observed by CCK8, colony formation, TUNEL staining and western blot assays. Bioinformatics tools discovered the targeting of suppressor of cancer cell invasion (SCAI) by miR-1825, which was further confirmed by luciferase reporter assay. Then the suppression of miR-1825 on SCAI protein expression was verified by western blotting. Eventually, rescue assays were implemented and affirmed the miR-1825/SCAI axis in PC cells. In conclusion, our present research disclosed the oncogenic role of miR-1825 and the miR-1825/SCAI pathway in PC. These findings gave new clues for the therapy of PC.

scholarly journals FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Zhang ◽  
Xian Zhang ◽  
Shasha Yang ◽  
Yanqiu Bao ◽  
Dongyuan Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Mesenchymal Transition

Abstract Background The expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer. Methods The Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan–Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and β-catenin activity was measured by a luciferase reporter system assay. Results Higher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of β-catenin and its downstream targets, p-GSK-3β and cyclin D1. Conclusion FOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/β-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.

scholarly journals Inhibition of cancer cell-derived exosomal microRNA-183 suppresses cell growth and metastasis in prostate cancer by upregulating TPM1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanping Dai ◽  
Xiaoqin Gao
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Emerging evidence continues to highlight the significant role of microRNAs (miRNAs) in the regulation of cancer growth and metastasis. Herein, the current study aimed to elucidate the role of exosomal miR-183 in prostate cancer development. Methods Initially, public microarray-based gene expression profiling of prostate cancer was employed to identify differentially expressed miRNAs. The putative target gene TPM1 of miR-183 was subsequently predicted, followed by the application of a luciferase reporter assay and examination of the expression patterns in prostate cancer patients and cell lines. The effects of miR-183 and TPM1 on processes such as cell proliferation, invasion and migration were evaluated using in vitro gain- and loss-of-function experiments. The effect of PC3 cells-derived exosomal miR-183 was validated in LNCaP cells. In vivo experiments were also performed to examine the effect of miR-183 on prostate tumor growth. Results High expression of miR-183 accompanied with low expression of TPM1 was detected in prostate cancer. Our data indicated that miR-183 could target and downregulate TPM1, with the overexpression of miR-183 and exosomal miR-183 found to promote cell proliferation, migration, and invasion in prostate cancer. Furthermore, the tumor-promoting effect of exosome-mediated delivery of miR-183 was subsequently confirmed in a tumor xenograft model. Conclusions Taken together, the key findings of our study demonstrate that prostate cancer cell-derived exosomal miR-183 enhance prostate cancer cell proliferation, invasion and migration via the downregulation of TPM1, highlighting a promising therapeutic target against prostate cancer.

scholarly journals miR-378a-5p inhibits the proliferation of colorectal cancer cells by downregulating CDK1

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai Li ◽  
Jieling Zhang ◽  
Mingkang Zhang ◽  
Yaohua Wu ◽  
Xinyu Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Target Gene ◽  
Cell Function ◽  
Luciferase Reporter ◽  
Colorectal Cancer Cells ◽  
Pathological Tissues

Abstract Background MicroRNAs (miRNAs) play an important role in tumor occurrence. The role of miR-378a-5p and CDK1 in colorectal cancer (CRC) was investigated in this study. Methods Investigation of TCGA database and the detection of miR-378a-5p expression in colorectal cancer pathological tissues and colorectal cancer cell lines were undertaken by using qRT-PCR. We performed cell function experiments (CCK-8 assay, EdU assay, colony formation assay, wound healing assay, transwell assay, cell apoptosis assessment, and cell cycle assessment) and nude mouse tumor formation experiments to evaluate the effects of miR-378a-5p on proliferation, metastasis, and invasion to explore the role of miR-378a-5p in vivo and in vitro. Next, through TCGA database, immunohistochemical staining of pathological tissues, and cell function experiments, the role of the target gene CDK1 of miR-378a-5p was verified by database prediction, and dual luciferase reporter gene experiments in colorectal cancer cells were performed. Finally, whether upregulation of CDK1 restores the inhibitory effect of overexpression of miR-378a-5p on the proliferation of CRC cells was studied by overexpression of CDK1. Results Bioinformatic analysis showed significant downregulation of miR-378a-5p levels in colorectal cancer (CRC). Cell function experiments and tumor xenograft mouse models confirmed the low expression of miR-378a-5p within CRC tissues, which indicated the tumor suppressive role of miR-378a-5p in CRC. To better explore the regulation of miR-378a-5p in CRC, we predicted and validated cell cycle-dependent protein kinase 1 (CDK1) as the miR-378a-5p target gene and observed that miR-378a-5p suppressed CRC cell proliferation by targeting CDK1. Conclusion The results of this study help to elucidate the mechanism by which miR-378a-5p can be used as a tumor marker to inhibit the growth of colorectal cancer and CDK1, which is related to the prognosis of colorectal cancer patients. MiR-378a-5p inhibits CRC cell proliferation by suppressing CDK1 expression, which may become a possible therapeutic target for treatment of CRC.

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