scholarly journals Long noncoding RNA Linc00337 functions as an E2F1 co-activator and promotes cell proliferation in pancreatic ductal adenocarcinoma

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Huakai Wang ◽  
Shiyong Yu ◽  
Huan Peng ◽  
Yijun Shu ◽  
Wenjie Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Ductal Adenocarcinoma ◽  
Regulation Mechanism ◽  
Clinical Value ◽  
Dismal Prognosis

Abstract Background Long noncoding RNA (lncRNA) Linc00337 has been implicated in lung, gastric, colorectal and esophageal squamous cell carcinoma progression via various mechanisms; however, its clinicopathological significance and role in pancreatic ductal adenocarcinoma (PDAC) progression remains largely unknown. Methods Multiple approaches such as bioinformatic analysis, Transfection, quantitative real-time-PCR, Western blotting, animal studies, RNA-immunoprecipitation (RIP), RNA-pulldown and RNA-Fluorescence in situ hybridization (RNA-FISH) and were utilized to explore the role of Linc00337 in PDAC. Results Here we identified Linc00337 is an oncogenic lncRNA during PDAC progression. We found that the expression of Linc00337 is elevated in PDAC tissues and the higher Linc00337 predicts dismal prognosis. Functionally, Linc00337 promotes PDAC cell proliferation and cell cycle transition both in vitro and in vivo. Mechanistically, Linc00337 binds to E2F1 and functions as an E2F1 coactivator to trigger the targets expression during PDAC progression. Conclusion Our results demonstrate a reciprocal regulation mechanism between Linc00337 and E2F1 in PDAC progression and report the clinical value of Linc00337 for PDAC prognosis and treatment.

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.

Lentivirus-Mediated RNA Interference Targeting the Long Noncoding RNA HOTAIR Inhibits Proliferation and Invasion of Endometrial Carcinoma Cells In Vitro and In Vivo

2014 ◽  
Vol 24 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Jiaming Huang ◽  
Peiqi Ke ◽  
Luyan Guo ◽  
Wei Wang ◽  
Hao Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Proliferation And Invasion

ObjectiveThe overexpression of long noncoding RNA HOTAIR is associated with various aggressive solid carcinomas. However, its relationship with endometrial carcinoma has not been reported. The present study aimed to investigate the expression of the long noncoding RNA HOTAIR in endometrial carcinoma, its relationship with the carcinoma’s clinicopathologic features, and the biological function of HOTAIR in regulating endometrial cancer cell proliferation and invasion in vitro and in vivo.MethodsThe expression of HOTAIR was detected in different tissues and cell lines by real-time PCR. Lentivirus-mediated HOTAIR-specific shRNAvectors were transfected into endometrial cancer HEC-1A cells. Cell proliferation and colony formation were examined by CCK-8 assays and colony formation assays, respectively. Invasion and migration were examined by Transwell assays. Flow cytometry assay was used to examine the cell cycle. In addition, xenograft model assays were performed to analyze the growth of endometrial cancer cells in vivo.ResultsOur data showed that HOTAIR expression was higher in endometrial cancer cells and tissues than in normal endometrial tissues. HOTAIR expression was closely related to the tumor stage (P= 0.045), myometrial invasion (P= 0.014), and lymph node metastasis (P= 0.033). The down-regulation of HOTAIR resulted in a significant inhibition of cell proliferation, migration, and invasion and in cell cycle arrest at the G0/G1 phase. Furthermore, HOTAIR depletion significantly suppressed the endometrial cancer tumorigenesis in vivo.ConclusionsThis study is the first to suggest that HOTAIR plays an important role in the carcinogenesis of endometrial cancer. Targeting HOTAIR may be a novel therapeutic strategy for endometrial cancer.

scholarly journals Long noncoding RNA H19 derived miR-675 regulates cell proliferation by down-regulating E2F-1 in human pancreatic ductal adenocarcinoma

2018 ◽  
Vol 9 (2) ◽  
pp. 389-399 ◽  
Author(s):  
Ling Ma ◽  
Xiaodong Tian ◽  
Huahu Guo ◽  
Zhengkui Zhang ◽  
Chong Du ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Ductal Adenocarcinoma

scholarly journals FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Taoyue Yang ◽  
Peng Shen ◽  
Qun Chen ◽  
Pengfei Wu ◽  
Hao Yuan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Lines ◽  
Rna Binding ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Pdac Cell

Abstract Background Circular RNAs (circRNAs) are becoming a unique member of non-coding RNAs (ncRNAs) with emerging evidence of their regulatory roles in various cancers. However, with regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation. Methods In our previous study, next-generation sequencing was used to identify differentially expressed circRNAs in 3 pairs of PDAC and adjacent normal tissues. Further validation of circRHOBTB3 expression in PDAC tissues and cell lines and gain-and-loss function experiments verified the oncogenic role of circRHOBTB3. The mechanism of circRHOBTB3 regulatory role was validated by pull-down assays, RIP, luciferase reporter assays. The autophagy response of PANC-1 and MiaPaca-2 cells were detected by mCherry-GFP-LC3B labeling and confocal microscopy, transmission electron microscopy and protein levels of LC3B or p62 via Western blot. Results circRHOBTB3 is highly expressed in PDAC cell lines and tissues, which also promotes PDAC autophagy and then progression in vitro and in vivo. Mechanistically, circRHOBTB3 directly binds to miR-600 and subsequently acts as a miRNA-sponge to maintain the expression level of miR-600-targeted gene NACC1, which facilitates the autophagy response of PDAC cells for adaptation of proliferation via Akt/mTOR pathway. Moreover, the RNA-binding protein FUS (FUS) directly binds to pre-RHOBTB3 mRNA to mediate the biogenesis of circRHOBTB3. Clinically, circRHOBTB3, miR-600 and NACC1 expression levels are correlated with the prognosis of PDAC patients and serve as independent risk factors for PDAC patients. Conclusions FUS-mediated circRHOBTB3 functions as a tumor activator to promote PDAC cell proliferation by modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.

scholarly journals Long Noncoding RNA AFAP1-AS1 Is a Critical Regulator of Nasopharyngeal Carcinoma Tumorigenicity

2020 ◽  
Vol 10 ◽  
Author(s):  
Min Fang ◽  
Minjun Zhang ◽  
Yiqing Wang ◽  
Fangqiang Wei ◽  
Jianhui Wu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Prognostic Indicator ◽  
Clinical Value ◽  
Interacting Protein ◽  
Mrna Stabilization

BackgroundThe long noncoding RNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is a critical player in various cancers. However, the clinical value and functional mechanisms of AFAP1-AS1 during the tumorigenicity of nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the clinical application and potential molecular mechanisms of AFAP1-AS1 in NPC tumorigenesis and progression.MethodsThe expression level of AFAP1-AS1 was determined by qRT-PCR in 10 paired fresh human NPC tissues and adjacent normal tissues. RNAscope was performed on 100 paired paraffin-embedded NPC and adjacent nontumor specimens. The biological functions of AFAP1-AS1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays were performed to detect and identify the AFAP1-AS1-interacting protein KAT2B. Protein-RNA immunoprecipitation (RIP) assays were conducted to examine the interaction of AFAP1-AS1 and KAT2B. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of transcription intermediary factor 1 alpha (TIF1α) and H3K14ac on the RBM3 promoter.ResultsAFAP1-AS1 is upregulated in NPC and is a poor prognostic indicator for survival in NPC patients. AFAP1-AS1 was required for NPC proliferation in vitro and tumorigenicity in vivo. Mechanistic investigations suggested that AFAP1-AS1 binds to KAT2B and promotes acetyltransferase activation at two residues (E570/D610). KAT2B further promotes H3K14 acetylation and protein binding to the bromo domain of TIF1α. Consequently, TIF1α acts as a nuclear transcriptional coactivator of RBM3 transcription, leading to YAP mRNA stabilization and enhanced NPC tumorigenicity.ConclusionsOur findings suggest that AFAP1-AS1 functions as an oncogenic biomarker and promotes NPC tumorigenicity through enhanced KAT2B acetyltransferase activation and YAP mRNA stabilization.

scholarly journals Long Noncoding RNA FEZF1-AS1 Promotes Osteosarcoma Progression by Regulating the miR-4443/NUPR1 Axis

2018 ◽  
Vol 26 (9) ◽  
pp. 1335-1343 ◽  
Author(s):  
Chengwei Zhou ◽  
Jianxiang Xu ◽  
Jinti Lin ◽  
Renjin Lin ◽  
Kai Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Mg63 Cells ◽  
Tumor Growth And Metastasis ◽  
And Migration

Long noncoding RNA (lncRNA) FEZF1-AS1 was demonstrated to facilitate cell proliferation and migration in some cancers. However, the functions of FEZF1-AS1 and its molecular mechanism in osteosarcoma remain to be elucidated. In our study, we found that the expression of FEZF1-AS1 was upregulated in osteosarcoma samples and cell lines compared with normal tissues or cells. Besides, we showed that the expression levels of FEZF1-AS1 in osteosarcoma patients were positively correlated with tumor metastasis and TNM stage. Additionally, FEZF1-AS1 knockdown inhibited cell proliferation, migration, and invasion in U2OS and MG63 cells, while upregulation had the opposite effects in vitro. Moreover, FEZF1-AS1 depletion inhibited tumor growth and metastasis in vivo. We found that FEZF1-AS1 sponged miR-4443 to promote NUPR1 expression in U2OS and MG63 cells. Furthermore, knockdown of miR-4443 abrogated FEZF1-AS1 silencing-induced inhibition of cell proliferation, migration, and invasion in osteosarcoma. Finally, we found that restoration of NUPR1 rescued the proliferation, migration, and invasion abilities of FEZF1-AS1-depleted U2OS and MG63 cells. Our study indicated that FEZF1-AS1 could promote osteosarcoma progression by sponging miR-4443 to promote NUPR1 expression. The FEZF1-AS1/miR-4443/NUPR1 axis may act as a novel therapeutic strategy for osteosarcoma treatment.

scholarly journals The long noncoding RNA LUCAT1 promotes colorectal cancer cell proliferation by antagonizing Nucleolin to regulate MYC expression

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Runliu Wu ◽  
Liang Li ◽  
Yang Bai ◽  
Bowen Yu ◽  
Canbin Xie ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Multiple Cancer ◽  
G Quadruplex

Abstract The long noncoding RNA (lncRNA) LUCAT1 was recently reported to be upregulated and to play an essential role in multiple cancer types, especially colorectal cancer (CRC), but the molecular mechanisms of LUCAT1 in CRC are mostly unreported. Here, a systematic analysis of LUACT1 expression is performed with data from TCGA database and clinic CRC samples. LUCAT1 is identified as a putative oncogene, which is significantly upregulated in CRC and is associated with poor prognosis. Loss of LUCAT1 restricts CRC proliferative capacities in vitro and in vivo. Mechanically, NCL is identified as the protein binding partner of LUCAT1 by using chromatin isolation by RNA purification coupled with mass spectrometry (ChIRP-MS) and RNA immunoprecipitation assays. We also show that NCL directly binds to LUCAT1 via its putative G-quadruplex-forming regions from nucleotides 717 to 746. The interaction between LUCAT1 and NCL interferes NCL-mediated inhibition of MYC and promote the expression of MYC. Cells lacking LUCAT1 show a decreased MYC expression, and NCL knockdown rescue LUCAT1 depletion-induced inhibition of CRC cell proliferation and MYC expression. Our results suggest that LUCAT1 plays a critical role in CRC cell proliferation by inhibiting the function of NCL via its G-quadruplex structure and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

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