scholarly journals LncRNA STXBP5-AS1 suppresses stem cell-like properties of pancreatic cancer by epigenetically inhibiting neighboring androglobin gene expression

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Shi Chen ◽  
Long Huang ◽  
Ge Li ◽  
Funan Qiu ◽  
Yaodong Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Annexin V ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Sphere Formation ◽  
Long Non Coding Rna

Abstract Previous studies suggest the tumor suppressor role of long non-coding RNA (lncRNA) STXBP5-AS1 in cervical and gastric cancer, but its expression pattern and functional mechanism are still elusive in pancreatic cancer (PC). Relative expression of STXBP5-AS1 in PC both in vivo and in vitro was analyzed by real-time PCR. IC50 of Gemcitabine was determined by the MTT assay. Cell proliferation in response to drug treatment was investigated by colony formation assay. Cell apoptosis was measured by both caspase-3 activity and Annexin V/PI staining. Cell invasion capacity was scored by the transwell assay in vitro, and lung metastasis was examined with the tail vein injection assay. Cell stemness was determined in vitro by sphere formation and marker profiling, respectively, and in vivo by limited dilution of xenograft tumor incidence. Subcellular localization of STXBP5-AS1 was analyzed with fractionation PCR. Association between STXBP5-AS1 and EZH2 was investigated by RNA-immunoprecipitation. The binding of EZH2 on ADGB promoter was analyzed by chromatin immunoprecipitation. The methylation was quantified by bisulfite sequencing. We showed downregulation of STXBP5-AS1 in PC associated with poor prognosis. Ectopic STXBP5-AS1 inhibited chemoresistance and metastasis of PC cells. In addition, STXBP5-AS1 compromised stemness of PC cells. Mechanistically, STXBP5-AS1 potently recruited EZH2 and epigenetically regulated neighboring ADGB transcription, which predominantly mediated the inhibitory effects of STXBP5-AS1 on stem cell-like properties of PC cells. Our study highlights the importance of the STXBP5-EZH2-ADGB axis in chemoresistance and stem cell-like properties of PC.

Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ling Zhou ◽  
Xiao-li Xu
Keyword(s):  
Cervical Cancer ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Injection Model ◽  
Rna Immunoprecipitation ◽  
Long Non Coding Rna

<b><i>Background:</i></b> Emerging research has demonstrated that long non-coding RNAs (lncRNAs) attach great importance to the progression of cervical cancer (CC). LncRNA ARAP1-AS1 was involved in the development of several cancers; however, its role in CC is far from being elucidated. <b><i>Methods:</i></b> Real-time PCR (RT-PCR) was employed to detect ARAP1-AS1 and miR-149-3p expression in CC samples. CC cell lines (HeLa and C33A cells) were regarded as the cell models. The biological effect of ARAP1-AS1 on cancer cells was measured using CCK-8 assay, colony formation assay, flow cytometry, Transwell assay and wound healing assay in vitro, and subcutaneous xenotransplanted tumor model and tail vein injection model in vivo. Furthermore, interactions between ARAP1-AS1 and miR-149-3p, miR-149-3p and POU class 2 homeobox 2 (POU2F2) were determined by bioinformatics analysis, qRT-PCR, Western blot, luciferase reporter and RNA immunoprecipitation assay, respectively. <b><i>Results:</i></b> The expression of ARAP1-AS1 was enhanced in CC samples, while miR-149-3p was markedly suppressed. Additionally, ARAP1-AS1 overexpression enhanced the viability, migration, and invasion of CC cells. ARAP1-AS1 downregulated miR-149-3p via sponging it. ARAP1-AS1 and miR-149-3p exhibited a negative correlation in CC samples. On the other hand, ARAP1-AS1 enhanced the expression of POU2F2, which was validated as a target gene of miR-149-3p. <b><i>Conclusion:</i></b> ARAP1-AS1 was abnormally upregulated in CC tissues and indirectly modulated the POU2F2 expression via reducing miR-149-3p expression. Our study identified a novel axis, ARAP1-AS1/miR-149-3p/POU2F2, in CC tumorigenesis.

scholarly journals The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer

2020 ◽  
Vol 21 (6) ◽  
pp. 2215
Author(s):  
Jiahui Li ◽  
Christopher Betzler ◽  
Philipp Lohneis ◽  
Marie Christine Popp ◽  
Jiwei Qin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
Stem Cell Markers ◽  
Sphere Formation

(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data (n = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC.

scholarly journals Long Non-Coding RNA MIR4435-2HG Promotes Glycolysis and Tumor Immunity in Pancreatic Cancer Through Absorption of microRNA-582-5p to Target GPX8

2021 ◽  
Author(s):  
Huimin Lu ◽  
Mao Li ◽  
Dujiang Yang ◽  
Zhenlu Li ◽  
Chao Yue ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Glutathione Peroxidase ◽  
Cell Lines ◽  
Tumor Immunity ◽  
Clinicopathological Characteristics ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Objective Long non-coding RNA MIR4435-2HG (MIR4435-2HG) has been clarified as a promoter in cancers, but its involvement in pancreatic cancer (PC) was not thoroughly probed. Methods MIR4435-2HG levels in PC clinical tissue and cell lines were analyzed. The relation between MIR4435-2HG levels with clinicopathological characteristics and survival of PC patients was evaluated. After transfection with plasmids altering MIR4435-2HG, microRNA (miR)-582-5p or glutathione peroxidase-8 (GPX8), the biological functions, glycolysis and tumor immunity of PANC-1 cells were observed. In vivo tumor growth was observed in nude mice. Results MIR4435-2HG was highly expressed in PC tissues and cell lines which was negatively correlated with clinicopathological characteristics and prognosis of PC patients. MIR4435-2HG or GPX8 inhibition or miR-582-5p elevation restrained the growth, glycolysis and immunity of PANC-1 cells. miR-582-5p down-regulation or GPX8 up-regulation reversed the effect of silenced MIR4435-2HG on PANC-1 cells. In vivo experiments further confirmed the in vitro results. Conclusion Our study highlights that MIR4435-2HG promotes glycolysis and tumor immunity in PC through absorption of micR-582-5p to target GPX8.

scholarly journals Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3145
Author(s):  
Karolin Walter ◽  
Eva Rodriguez-Aznar ◽  
Monica S. Ventura Ferreira ◽  
Pierre-Olivier Frappart ◽  
Tabea Dittrich ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Biology ◽  
Telomerase Activity ◽  
Pancreatic Cancer Cells ◽  
Sphere Formation ◽  
Telomerase Regulation ◽  
Pancreatic Cancer Stem Cells

To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.

scholarly journals A KRAS-responsive long non-coding RNA controls microRNA processing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lei Shi ◽  
Peter Magee ◽  
Matteo Fassan ◽  
Sudhakar Sahoo ◽  
Hui Sun Leong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Lung Tumorigenesis ◽  
Downstream Signaling ◽  
Non Coding Rna ◽  
Microrna Processing ◽  
Long Non Coding Rna

AbstractWild-type KRAS (KRASWT) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRASWT overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically, KIMAT1 is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex. KIMAT1 knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for KIMAT1 in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with KIMAT1 could be a strategy to hamper KRAS-induced tumorigenesis.

scholarly journals A Concise Review on the Role of CircPVT1 in Tumorigenesis, Drug Sensitivity, and Cancer Prognosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Tayyebeh Khoshbakht ◽  
Mohammad Taheri ◽  
Elena Jamali
Keyword(s):  
Circular Rna ◽  
Cancer Prognosis ◽  
Genomic Locus ◽  
Non Coding Rna ◽  
Clinical Investigations ◽  
Cancer Types ◽  
Long Non Coding Rna

CircPVT1 (hsa_circ_0001821) is a cancer-related circular RNA (circRNA) that originated from a genomic locus on chromosome 8q24. This locus has been previously found to encode the oncogenic long non-coding RNA PVT1. Expression of this circRNA has been found to be upregulated in diverse neoplastic conditions. CircPVT1 acts as a sponge for miR-125a, miR-125b, miR-124-3p, miR-30a-5p, miR-205-5p, miR‐423‐5p, miR‐526b, miR-137, miR-145-5p, miR-497, miR-30d/e, miR-455-5p, miR-29a-3p, miR-204-5p, miR-149, miR-106a-5p, miR-377, miR-3666, miR-203, and miR-199a-5p. Moreover, it can regulate the activities of PI3K/AKT, Wnt5a/Ror2, E2F2, and HIF-1α. Upregulation of circPVT1 has been correlated with decreased survival of patients with different cancer types. In the current review, we explain the oncogenic impact of circPVT1 in different tissues based on evidence from in vitro, in vivo, and clinical investigations.

scholarly journals Long non-coding RNA PSMA3-AS1 enhances cell proliferation, migration and invasion by regulating miR-302a-3p/RAB22A in glioma

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Li-li Zhou ◽  
Meng Zhang ◽  
Yan-zhen Zhang ◽  
Mei-fen Sun
Keyword(s):  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Nude Mouse Model ◽  
Cell Behaviors ◽  
Non Coding Rna ◽  
The Central Nervous System ◽  
Long Non Coding Rna

Abstract Glioma is the most prevalent solid tumor in the central nervous system (CNS). Recently, it has been indicated that long non-coding RNAs (lncRNAs) substantially adjust the development of a variety of human cancers. In the present study, it was found and verified via microarray analysis that lncRNA PSMA3-AS1 exhibited a high expression in glioma tissues and cell lines. Then CCK-8, 5-Ethynyl-2′-deoxyuridine (EdU) staining, plate clone assay, Transwell assay, Western blotting and nude mouse model were adopted to verify PSMA3-AS1’s effects on glioma. Knockdown of PSMA3-AS1 inhibited the migration, proliferation and invasion of glioma cells in vivo and in vitro. Besides, PSMA3-AS1 bound to miR-302a-3p directly reduced the expression of miR-302a-3p, thus functioning as an endogenous sponge confirmed by luciferase reporter assay and bioinformatics analysis. PSMA3-AS1 knockdown remarkably enhanced the role of miR-302a-3p overexpression in cell behaviors in glioma. Moreover, these assays also confirmed that RAB22A was a target of miR-302a-3p. In this research, therefore, the PSMA3-AS1/miR-302a-3p/RAB22A pathway regulatory axis may be revealed in the pathogenesis of glioma, and PSMA3-AS1 can be used as an underlying target for the treatment and prognosis of glioma.

scholarly journals The long non-coding RNA HOXA11-AS activates ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liting You ◽  
Qian Wu ◽  
Zhaodan Xin ◽  
Huiyu Zhong ◽  
Juan Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
And Function ◽  
Long Non Coding Rna ◽  
Invasion Assays

Abstract Background miR-124-3p can inhibit integrin β3 (ITGB3) expression to suppress the migration and invasion of gastric cancer (GC), and in the process lncRNA HOXA11-AS may act as a molecular sponge. Methods Luciferase reporter assay was conducted to verify the binding of miR-124-3p and HOXA11-AS. RT-PCR and western blot were performed to detect the expression of HOXA11-AS, miR-124-3p and ITGB3 in GC tissues and cells. Gene silence and overexpression experiments as well as cell migration and invasion assays on GC cell lines were performed to determine the regulation of molecular pathways, HOXA11-AS/miR-124-3p/ITGB3. Furthermore, the role of HOXA11-AS in GC was confirmed in mice models. Results We found HOXA11-AS is up-regulated in GC tissues and can bind with miR-124-3p. Through overexpression/knockdown experiments and function tests in vitro, we demonstrated HOXA11-AS can promote ITGB3 expression by sponging miR-124-3p, consequently enhance the proliferation, migration, and invasion of GC cells. Meanwhile, we validated that HOXA11-AS promotes migration and invasion of GC cells via down-regulating miR-124-3p and up-regulating ITGB3 in vivo. Conclusions We demonstrated that lncRNA HOXA11-AS can increase ITGB3 expression to promote the migration and invasion of gastric cancer by sponging miR-124-3p. Our results suggested that HOXA11-AS may reasonably serve as a promising diagnostic biomarker and a potential therapeutic target of GC.

scholarly journals Enzalutamide-Induced Upregulation of PCAT6 Promotes Prostate Cancer Neuroendocrine Differentiation by Regulating miR-326/HNRNPA2B1 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Liu ◽  
Hui-Yang Jiang ◽  
Tao Yuan ◽  
Jie Luo ◽  
Wei-Dong Zhou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Neuroendocrine Differentiation ◽  
Underlying Mechanism ◽  
Non Coding Rna ◽  
Metastasis Model ◽  
Long Non Coding Rna

Our previous studies have demonstrated that Enzalutamide-induced upregulation of long non-coding RNA p21 (lncRNA-p21) facilitates prostate cancer (PCa) neuroendocrine differentiation (NED). Given the important role of lncRNAs in PCa pathogenesis, and given that lots of lncRNAs are dys-regulated in neuroendocrine PCa (NEPC) patients, we next explored the biological function and underlying mechanism of lncRNA-PCAT6 (PCAT6) in mediating Enzalutamide-induced NED. The level of PCAT6 in Enzalutamide-treated PCa cells and NEPC samples were assessed using quantitative RT-PCR (qPCR). The effect of PCAT6 on PCa cell proliferation, invasion, and NED was evaluated through CCK-8, transwell, qPCR, western blot analysis, Xenograft mouse model, and in vivo lung metastasis model. We found that PCAT6 was highly expressed in NE-like cells (PC3, DU145, and NCI-H660) compared with androgen-sensitive LNCaP cells. PCAT6 was also highly expressed in NEPC tissues. Enzalutamide treatment resulted in a significant increase of PCAT6 level in a dose- and time-dependent fashion. Functionally, PCAT6 overexpression promoted NED of C4-2 cells, as evidenced by an increased expression of NE markers (NSE, ChgA, and SYP), whereas PCAT6 knockdown in NCI-H661 cells repressed NED. Furthermore, PCAT6 overexpression promoted PCa cell proliferation and invasion in vitro and in vivo. Mechanistically, PCAT6 functioned as competing endogenous (ce) RNA via absorbing miR-326, thus resulting in a de-suppression of Hnrnpa2b1 target gene. The current results demonstrate that PCAT6 acted as a tumor activator in PCa progression by sponging miR-326 and increasing Hnrnpa2b1 expression and that the PCAT6/miR-326/Hnrnpa2b1 signaling might be a new therapeutic target for PCa.

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