scholarly journals LncRNA GAS8-AS1 is a Novel Prognostic and Diagnostic Biomarker for Pancreatic Cancer

2021 ◽  
Author(s):  
Ling Zhang ◽  
Miao Li ◽  
Lihong Deng ◽  
Dujiang Yang ◽  
Chao Yue ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Plasma Levels ◽  
Early Stage ◽  
Migration And Invasion ◽  
Cell Transfection ◽  
Healthy Controls ◽  
Overall Survival Rate ◽  
Diagnostic Biomarker ◽  
Real Time Quantitative Pcr

Abstract Background: LncRNA GAS8-AS1 inhibits thyroid carcinoma, but its function in other malignancies is unknown. The present study aimed to investigate the involvement of GAS8-AS1 in pancreatic cancer (PC). Methods: The present study included 68 PC patients (38 males and 30 females, 42- 66 years, 52.1±4.5) and 62 healthy volunteers (28 males and 24 females, 43- 67 years, 52.3 ±4.9). Real-time quantitative PCR, transient cell transfection and in vitro cell migration and invasion assay were applied for the research. In the present study we found that plasma GAS8-AS1 was lower in PC patients than in healthy controls. Downregulation of plasma GAS8-AS1 distinguished early stage PC patients from healthy controls. Results: Patients with low plasma levels of GAS8-AS1 showed significantly lower 5-year overall survival rate. Plasma levels of miR-1179 were also significantly lower in PC patients than in healthy controls, and were positively correlated with plasma levels of GAS8-AS1 only in PC patients. GAS8-AS1 overexpression resulted in the upregulation of miR-1179. MiR-1179 overexpression also led to the overexpression of GAS8-AS1. Overexpression of both GAS8-AS1 and miR-1179 led to inhibited migration and invasion of PC cells. Conclusions: Therefore, GAS8-AS1 may promote PC by positively interacting with miR-1179.

Homeobox-A13 acts as a functional prognostic and diagnostic biomarker via regulating P53 and Wnt signaling pathways in lung cancer

2021 ◽  
pp. 1-16
Author(s):  
Yang Wang ◽  
Bo He ◽  
Yan Dong ◽  
Gong-Jin He ◽  
Xiao-Wei Qi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Feature ◽  
Diagnostic Biomarker

BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/β-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/β-catenin signaling pathways.

scholarly journals Mechanism of LIN28B in Trophoblastic Villous Cells of Unexplained Recurrent Abortion

2021 ◽  
Author(s):  
QiaoYao Huang ◽  
YanRu Niu ◽  
LiJun Song ◽  
JinZhi Huang ◽  
Chenxi Wang ◽  
...  
Keyword(s):  
Negative Control ◽  
Cellular Level ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Akt Phosphorylation ◽  
Real Time Quantitative Pcr ◽  
Villous Trophoblast

Abstract Background: LIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. To verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA(unexplained recurrent spontaneous abortion)and artificial termination of pregnancy (negative control, NC). Methods:The Lin28b gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function.Results: The expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia. Conclusions: LIN28B can inhibit cell proliferation, invasion and migration in vitro, and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study.

scholarly journals Does LIN28B gene dysregulation make women more likely to abort?

2021 ◽  
Author(s):  
QiaoYao Huang ◽  
YanRu Niu ◽  
LiJun Song ◽  
JinZhi Huang ◽  
Chenxi Wang ◽  
...  
Keyword(s):  
Negative Control ◽  
Cellular Level ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Akt Phosphorylation ◽  
Real Time Quantitative Pcr ◽  
Villous Trophoblast

Background: LIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. To verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA(unexplained recurrent spontaneous abortion)and artificial termination of pregnancy (negative control, NC). Methods:The Lin28b gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function. Results: The expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia. Conclusions: LIN28B can inhibit cell invasion and migration in vitro, and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study.

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.

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

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.

A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes

2021 ◽  
Author(s):  
Hoonsik Nam ◽  
Sunmi Kang ◽  
Min Seok Park ◽  
Suyeon Kang ◽  
Han Sun Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Normal Cell ◽  
Diagnostic Performance ◽  
Early Stage ◽  
Serum Marker ◽  
Diabetic Patients ◽  
Diagnostic Biomarker ◽  
Diabetic Status ◽  
Validation Set

Abstract Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

scholarly journals LncRNA PAPAS may promote triple-negative breast cancer by downregulating miR-34a

2019 ◽  
Vol 47 (8) ◽  
pp. 3709-3718 ◽  
Author(s):  
Yan Kong ◽  
Cuizhi Geng ◽  
Qian Dong
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cancer Biology ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Healthy Controls ◽  
Plasma Samples

Objective To investigate the role of promoter and pre-rRNA antisense (PAPAS) long noncoding (Lnc) RNA in cancer biology. Methods Tumour and tumour-adjacent healthy tissue biopsies from patients with triple-negative breast cancer (TNBC), and plasma samples from these patients plus healthy controls, were assessed for PAPAS and microRNA (miR)-34a. Effects of PAPAS and miR-34a overexpression were also investigated in vitro. Results PAPAS was upregulated in tumour tissues of patients with TNBC versus tumour-adjacent healthy tissues. Plasma PAPAS levels were also upregulated in patients with TNBC versus healthy controls. Levels of PAPAS in tumour tissue was significantly positively correlated with PAPAS levels in plasma from patients with TNBC. MiR-34a was downregulated in tumour tissues versus adjacent healthy tissues, and was significantly correlated with PAPAS in tumour tissues. PAPAS overexpression in vitro was associated with miR-34a inhibition, while miR-34a failed to significantly affect PAPAS levels. PAPAS overexpression promoted in vitro migration and invasion of TNBC cells, while miR-34a overexpression was inhibitory. MiR-34a overexpression decreased the enhanced cell migration and invasion associated with PAPAS overexpression. PAPAS overexpression showed no significant effects on cancer-cell proliferation. Conclusion LncRNA PAPAS may promote TNBC by downregulating miR-34a.

scholarly journals β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial–Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

2019 ◽  
Vol 9 ◽  
Author(s):  
Zhang-qi Cao ◽  
Xue-xi Wang ◽  
Li Lu ◽  
Jing-wen Xu ◽  
Xiao-bin Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Combined Treatment ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Cancer Activity

β-sitosterol (BS), a major bioactive constituent present in plants, has shown potent anti-cancer activity against many human cancer cells, but its activity in pancreatic cancer (PC) cells has rarely been reported. Gemcitabine (GEM) is one of the first-line drugs for PC therapy, however, the treatment effect is not sustained due to prolonged drug resistance. In this study, we firstly studied the anti-PC activity and the mechanism of BS alone and in combination with GEM in vitro and in vivo. BS effectively inhibited the growth of PC cell lines by inhibiting proliferation, inducing G0/G1 phase arrest and apoptosis, suppressed the NF- kB activity, and increased expression of the protein Bax but decreased expression of the protein Bcl-2. Moreover, BS inhibited migration and invasion and downregulated epithelial–mesenchymal transition (EMT) markers and AKT/GSK-3β signaling pathways. Furthermore, the combination of BS and GEM exhibited a significant synergistic effect in MIAPaCa-2 and BXPC-3 cells. More importantly, the combined treatment with BS and GEM lead to significant growth inhibition of PC xenografts. Overall, our data revealed a promising treatment option for PC by the combination therapy of BS and GEM.

scholarly journals Down-regulation of lncRNA-NEF indicates poor prognosis in intrahepatic cholangiocarcinoma

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhanqiang Liang ◽  
Bingshuai Zhu ◽  
Dongdong Meng ◽  
Xiwen Shen ◽  
Xuemin Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Intrahepatic Cholangiocarcinoma ◽  
Plasma Levels ◽  
Migration And Invasion ◽  
Healthy Controls ◽  
Cancer Cell Migration ◽  
Down Regulation ◽  
Expression Levels ◽  
Tumor Tissues

Abstract LncRNA-NEF is a tumor suppressor lncRNA in liver cancer. The present study aimed to investigate the role of lncRNA-NEF in intrahepatic cholangiocarcinoma (IHCC), which is second most common type of primary cancer of the hepatobiliary system that causes high mortality rate. In the present study we found that lncRNA-NEF was down-regulated, while Runt-related transcription factor 1 (RUNX1) was up-regulated in tumor tissues than in adjacent healthy tissues of IHCC patients. Expression levels of lncRNA-NEF and RUNX1 were significantly and reversely correlated in tumor tissues but not in adjacent healthy tissues. Plasma levels of lncRNA-NEF were significantly lower in IHCC patients than in healthy controls. Down-regulation of lncRNA-NEF effectively distinguished stage I and II IHCC patients from healthy controls. Patients were followed up for 5 years, patients with high plasma levels of lncRNA-NEF showed significantly better survival conditions compared with patients with low expression levels of lncRNA-NEF. LncRNA-NEF overexpression led to inhibited expression of RUNX1 in cells of IHCC cell lines and inhibited cancer cell migration and invasion. In contrast, RUNX1 overexpression showed no significant effects on lncRNA-NEF expression, but attenuated the effects of lncRNA-NEF overexpression on cancer cell migration and invasion. We therefore concluded that lncRNA-NEF participated in IHCC possibly by interacting with RUNX1.

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