scholarly journals Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Youliang Wu ◽  
Delong Meng ◽  
Xin Xu ◽  
Junjun Bao ◽  
Yexiang You ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Functional Characterization ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Human Gallbladder ◽  
Normal Gallbladder ◽  
Degree Of Differentiation

Abstract Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

scholarly journals Expression and Functional Identification of INPP4B in Gallbladder Cancer Patients and Gallbladder Cancer Cells

2020 ◽  
Author(s):  
Youliang Wu ◽  
Delong Meng ◽  
Xin Xu ◽  
Junjun Bao ◽  
Yexiang You ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Negative Regulator ◽  
Inositol Polyphosphate ◽  
Functional Identification ◽  
Human Gallbladder ◽  
Apoptosis Detection ◽  
Normal Gallbladder

Abstract Purpose: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of PI3K-Akt signaling pathway and plays a contradictory role in different types of cancers. However, its biological role in human gallbladder cancer (GBC) remain unclear. Here we aimed to investigate the expression, clinical significance and biological function of INPP4B in GBC clinical dates and GBC cell lines. Methods: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analyzed. Knockdown and overexpression of INPP4B on GBC-SD and SGC-996 cells were used to identify INPP4B function in vitro, using cell proliferation assay, clonogenic assay, apoptosis detection, cratch wound-healing assay and transwell assay.Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues, and was related to histopathological differentiation. Here, we observed that INPP4B was highly expressed in high-moderate differentiated compared to low-undifferentiated. Additionally, we found that INPP4B expression was not associated with overall survival in GBC patients and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and prognosis of GBC from histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression at different degrees of differentiation. In addition, INPP4B knockdown inhibited tumorigenicity in vitro, and INPP4B overexpression induced tumorigenicity in vitro, which may play a role as an oncoprotein.Conclusions: These findings implicated that INPP4B may play a dual role in the prognosis of GBC with different degrees of differentiation, and might act as an oncogene in gallbladder cancer cells.

Identification of miR-885-5p as a tumor biomarker: regulation of cellular function in cervical cancer

2021 ◽  
Author(s):  
Yuanqi Zu ◽  
Qianqian Wang ◽  
Hong Wang
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Migration And Invasion ◽  
Rank Test ◽  
Tumor Biomarker ◽  
Cancer Tissue ◽  
Cervical Cancer Cells ◽  
Tissue Specimens

Objectives: MicroRNAs were revealed as biomarkers for early detection or prognosis predictors of cancer and were involved in the progression of cancer. The present study investigated the expression pattern, potential clinical, and functional role of miR-885-5p in cervical cancer. Design: A total of 115 pairs of cervical cancer tissue specimens and adjacent non-tumor paracancerous tissue specimens were collected from the cervical cancer patients who underwent surgical resection or biopsy without preoperative systemic therapy at Maternity and Child Health Care of Zaozhuang from 2012 to 2014. Participants/Materials, Setting, Methods: The expression levels of miR-885-5p in cervical cancer were measured using the qRT-PCR assay. A follow-up study was conducted and the Kaplan-Meier method with log-rank test was used to analyze the potential clinical significance of miR-885-5p in cervical cancer. The functional experiments including CCK-8, Transwell migration, and invasion assays were used to investigate the biological function of miR-885-5p in cervical cancer cells. Results: miR-885-5p expression was decreased in tumor tissues and tumor cell lines compared to normal control. Low expression of miR-885-5p was related to lymph node metastasis, late FIGO stage, and shorter overall survival outcome. Ascending expression of miR-885-5p inhibited the proliferative, migratory, and invasive abilities of cervical cancer cells, while downregulation of miR-885-5p promoted these cellular abilities of cervical cancer cells in vitro. Limitations: The patient population size was limited, thus the clinical significance of miR-885-5p requires further verification. Secondly, the precise mechanism of miR-885-5p in cervical cancer still exclusive. In future studies, a larger sample size will be required to confirm the prognostic value of miR-885-5p in cervical cancer, and the possible targets, as well as the detailed mechanism of miR-885-5p, will be investigated. Conclusions: miR-885-5p expression was decreased in cervical cancer and downregulation of miR-885-5p promoted the progression of cervical cancer cells. miR-885-5p may be an independent prognostic predictor and therapeutic target for treating cervical cancer.

scholarly journals Osthole inhibits the progression of human gallbladder cancer cells through JAK/STAT3 signal pathway both in vitro and in vivo

2019 ◽  
Vol 30 (10) ◽  
pp. 1022-1030 ◽  
Author(s):  
Tian Le Zou ◽  
Hong Fei Wang ◽  
Tai Ren ◽  
Zi Yu Shao ◽  
Rui Yan Yuan ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Cells ◽  
Signal Pathway ◽  
Human Gallbladder

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

scholarly journals RasOncogene-Mediated Progressive Silencing of Extracellular Superoxide Dismutase in Tumorigenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Francesca Cammarota ◽  
Gabriella de Vita ◽  
Marco Salvatore ◽  
Mikko O. Laukkanen
Keyword(s):  
Superoxide Dismutase ◽  
Cancer Cells ◽  
Self Regulation ◽  
Thyroid Cell ◽  
Extracellular Superoxide Dismutase ◽  
Mrna Synthesis ◽  
Ras Activation ◽  
Degree Of Differentiation ◽  
In Cells

Extracellular superoxide dismutase (SOD3) is a secreted enzyme that uses superoxide anion as a substrate in a dismutase reaction that results in the formation of hydrogen peroxide. Both of these reactive oxygen species affect growth signaling in cells. Although SOD3 has growth-supporting characteristics, the expression ofSOD3is downregulated in epithelial cancer cells. In the current work, we studied the mechanisms regulatingSOD3expressionin vitrousing thyroid cell models representing different stages of thyroid cancer. We demonstrate that a low level of RAS activation increasesSOD3mRNA synthesis that then gradually decreases with increasing levels of RAS activation and the decreasing degree of differentiation of the cancer cells. Our data indicate thatSOD3regulation can be divided into two classes. The first class involves RAS–driven reversible regulation ofSOD3expression that can be mediated by the following mechanisms: RAS GTPase regulatory genes that are responsible forSOD3self-regulation; RAS-stimulated p38 MAPK activation; and RAS-activated increased expression of themir21microRNA, which inversely correlates withsod3mRNA expression. The second class involves permanent silencing ofSOD3mediated by epigenetic DNA methylation in cells that represent more advanced cancers. Therefore, the work suggests thatSOD3belongs to the group ofrasoncogene-silenced genes.

scholarly journals Long Non-coding RNA DLEU2L Targets miR-210-3p to Suppress Gemcitabine Resistance in Pancreatic Cancer Cells via BRCA2 Regulation

2021 ◽  
Vol 8 ◽  
Author(s):  
Fei Xu ◽  
Heshui Wu ◽  
Jiongxin Xiong ◽  
Tao Peng
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Migration And Invasion ◽  
Pancreatic Cell ◽  
Clinical Issue ◽  
Pancreatic Cancer Cells

Gemcitabine (GEM) resistance remains a challenging clinical issue to overcome in chemotherapy against pancreatic cancer. We previously demonstrated that miR-210 derived from pancreatic cancer stem cells enhanced the GEM-resistant properties of pancreatic cancer cells, thus identifying miR-210 as an oncogenic miRNA. Herein, we report the existence of an upstream effector that acts as a competing endogenous RNA (ceRNA) to miR-210. Bioinformatic screening was performed to identify lncRNAs with a binding relationship to miR-210. Overexpression and interference vectors were constructed to demonstrate the effect of ceRNA activity in pancreatic cell behavior, both in vitro and in vivo. DLEU2L (deleted in lymphocytic leukemia 2-like), which is expressed at low levels in pancreatic cancer tissues, was shown to exhibit a binding relationship with miR-210-3p. Overexpression of DLEU2L and silencing of miR-210-3p suppressed the proliferation, migration, and invasion of pancreatic cancer cells while promoting apoptosis. These effects occurred via the inhibition of the Warburg effect (aerobic glycolysis) and AKT/mTOR signaling. In addition, we showed that BRCA2 is a target gene of miR-210-3p, and the downregulation of miR-210-3p by DLEU2L effectively induced an upregulation of BRCA2 via the ceRNA mechanism. In vivo, DLEU2L overexpression and miR-210-3p interference suppressed pancreatic tumor progression, consistent with the results of in vitro studies. The findings of our study establish DLEU2L as a ceRNA to miR-210-3p and reveal the critical role of the DLEU2L/miR-210-3p crosstalk in targeting GEM resistance.

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