Long Noncoding RNA OIP5-AS1 Promotes the Disease Progression in Nasopharyngeal Carcinoma by Targeting miR-203

Nasopharyngeal carcinoma (NPC) is a kind of malignancy generated from the nasopharyngeal epithelium. Recently, long noncoding RNA (lncRNA) has been shown to be involved in the regulation of many signaling pathways and is closely associated with carcinogenesis and tumor progression. However, the precise role of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in NPC is not well understood. Here, we find that OIP5-AS1 is overexpressed in NPC patient specimens and NPC cell lines. Further investigations reveal that knockdown of OIP5-AS1 significantly inhibits the proliferation, migration, and invasion and accelerates the apoptosis of NPC cells in vitro. Consistent with these findings, NPC progression is significantly slowed in mice when OIP5-AS1 is knocked down. Interestingly, there is a functional link between OIP5-AS1 and microRNA-203 (miR-203), a tumor suppressor, in NPC cells. In conclusion, our data demonstrate that OIP5-AS1 plays an important role in the development and progression of NPC by targeting miR-203 and therefore provide a promising target for the treatment of NPC.

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

Frontiers in Oncology ◽

10.3389/fonc.2020.601055 ◽

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.

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PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22041882 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1882

Author(s):

Abdelrahman M. Elsayed ◽

Emine Bayraktar ◽

Paola Amero ◽

Salama A. Salama ◽

Abdelaziz H. Abdelaziz ◽

...

Keyword(s):

Mouse Model ◽

Long Noncoding Rna ◽

Proteomic Analysis ◽

Noncoding Rna ◽

Mtor Pathway ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Physical Interaction ◽

Cisplatin Sensitivity

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

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LncRNA GHET1 Promotes Esophageal Squamous Cell Carcinoma Cells Proliferation and Invasion via Induction of EMT

The International Journal of Biological Markers ◽

10.5301/ijbm.5000304 ◽

2017 ◽

Vol 32 (4) ◽

pp. 403-408 ◽

Cited By ~ 22

Author(s):

Hongfen Liu ◽

Qiang Zhen ◽

Yakun Fan

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Noncoding Rna ◽

In Vitro Assays ◽

Migration And Invasion ◽

Advanced Tumor

Background Recent studies have shown that long noncoding RNA (IncRNA) gastric carcinoma highly expressed transcript 1 (GHET1) was involved in the progression of tumors. However, the role of GHET1 in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods The expression of IncRNA GHET1 was examined in 55 paired ESCC tissues and adjacent nontumor tissues. Molecular and cellular techniques were used to explore the role of GHET1 on ESCC cells. Results Our data showed that GHET1 expression was significantly increased in ESCC tissues and cell lines. High GHET1 expression in ESCC tissues was significantly associated with poor differentiation, advanced tumor nodes metastasis stage, and lymph node metastasis. GHET1 showed high sensitivity and specificity for diagnosing ESCC. Our data from in vitro assays showed that GHET1 inhibition suppressed ESCC cells proliferation, migration, and invasion, and induced cells apoptosis. Furthermore, western blot showed that GHET1 inhibition significantly decreased the expression of vimentin and N-cadherin while it increased the expression of E-cadherin. Conclusions Our study indicates that GHET1 acts as an oncogene in ESCC and may represent a novel therapeutic target for the treatment of ESCC patients.

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circATP2A2 promotes osteosarcoma progression by upregulating MYH9

Open Medicine ◽

10.1515/med-2021-0370 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1749-1761

Author(s):

Xin Cao ◽

Xianfeng Meng ◽

Peng Fu ◽

Lin Wu ◽

Zhen Yang ◽

...

Keyword(s):

Cell Proliferation ◽

Area Under Curve ◽

Prognostic Biomarker ◽

Migration And Invasion ◽

Promising Target ◽

Repressive Effect ◽

Cell Malignancy

Abstract Osteosarcoma (OS) is a highly metastatic primary malignant tumor. CircRNA hsa_circ_0028173 (circATP2A2) has been uncovered to be related to the advancement of OS. However, the biological role of circATP2A2 in OS has not been validated. circATP2A2 and MYH9 were upregulated while miR-335-5p was downregulated in OS. OS patients with high circATP2A2 expression displayed a shorter overall survival and the area under curve of circATP2A2 was 0.77, manifesting that circATP2A2 might be a diagnostic and prognostic biomarker. circATP2A2 silencing repressed OS cell proliferation and glycolysis in vivo and constrained OS cell proliferation, glycolysis, migration, and invasion in vitro. circATP2A2 regulated MYH9 expression through sponging miR-335-5p. MiR-335-5p inhibitor reversed the repressive effect of circATP2A2 knockdown on OS cell malignancy and glycolysis. MYH9 overexpression overturned miR-335-5p upregulation-mediated OS cell malignancy and glycolysis. circATP2A2 accelerated OS cell malignancy and glycolysis through upregulating MYH9 via sponging miR-335-5p, offering a promising target for OS treatment.

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The Long Noncoding RNA TUG1 Promotes Laryngeal Cancer Proliferation and Migration

Cellular Physiology and Biochemistry ◽

10.1159/000493876 ◽

2018 ◽

Vol 49 (6) ◽

pp. 2511-2520 ◽

Cited By ~ 17

Author(s):

Zhonghua Zhang ◽

Xuehai Wang ◽

Shengda Cao ◽

Xiao Han ◽

Zhanwang Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Cell Cycle Progression ◽

Clinical Stage ◽

Migration And Invasion ◽

Cancer Proliferation

Background/Aims: Researchers have shown that long noncoding RNAs are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). However, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in the pathogenesis of LSCC remains unclear, although it is recognized as an oncogenic regulator for several types of squamous cell carcinoma. Methods: qRT-PCR was performed to measure the expression of TUG1 in LSCC tissues and cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to measure the effect of TUG1 on cell proliferation. Transwell assay and flow cytometry were employed to determine the effect of TUG1 on cell migration and invasion. Western-blot were performed to explore the relation of TUG1 and p53 mRNA. Results: Higher TUG1 expression in LSCC than in paired normal tumor-adjacent tissue specimens (N = 64) was observed using quantitative real-time polymerase chain reaction. Also, high TUG1 expression was positively associated with advanced T category, worse lymph node metastasis and late clinical stage. Furthermore, in vitro experiments demonstrated that silencing of TUG1 markedly inhibited proliferation, cell-cycle progression, migration, and invasion of LSCC cells, whereas depletion of TUG1 led to increased apoptosis. Conclusion: These findings demonstrated that upregulated TUG1 expression exerted oncogenic effects by promoting proliferation, migration, and invasion, and inhibiting apoptosis in LSCC cells.

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Knockdown of Long Noncoding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Inhibits Proliferation, Migration, and Invasion and Promotes Apoptosis by Targeting miR-124 in Retinoblastoma

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x14953948675403 ◽

2018 ◽

Vol 26 (4) ◽

pp. 581-591 ◽

Cited By ~ 16

Author(s):

Shujun Liu ◽

Guigang Yan ◽

Junfu Zhang ◽

Lianzhi Yu

Keyword(s):

Lung Adenocarcinoma ◽

Cell Viability ◽

Cell Line ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Migration And Invasion ◽

Erk Mapk ◽

Underlying Mechanisms ◽

Y79 Cells

Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line (p < 0.01). Moreover, MALAT1 silence inhibited cell viability, migration, and invasion and promoted apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). miR-124 was upregulated by MALAT1 silence and hence was identified as a target of MALAT1 (p < 0.05 or p < 0.001). In addition, miR-124 suppression inhibited cell apoptosis and remarkably abolished the inhibitory effects of MALAT1 silence on cell viability, migration, and invasion (p < 0.05, p < 0.01, or p < 0.001). In addition, Slug was a target of miR-124 and regulated cell viability, migration, invasion, and apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). Further, Slug silence abolished miR-124 suppression-induced inactivation of the ERK/MAPK and Wnt/β-catenin pathways. Taken together, our data highlight the pivotal role of MALAT1 in RB. Moreover, the present study elucidated the MALAT1‐miR-124‐ERK/MAPK and Wnt/β-catenin signaling pathways in RB, which might provide a new approach for the treatment of RB.

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The Long Noncoding RNA HOTAIR Promotes Colorectal Cancer Progression by Sponging miR-197

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15105708598531 ◽

2018 ◽

Vol 26 (3) ◽

pp. 473-481 ◽

Cited By ~ 18

Author(s):

Xinyang Lu ◽

Zhiqiang Liu ◽

Xiaofei Ning ◽

Lunhua Huang ◽

Biao Jiang

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Migration And Invasion ◽

Downstream Target ◽

Potential Applications ◽

Colorectal Cancer Progression

The long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer was detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration, and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.

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Long noncoding RNA WEE2-AS1 plays an oncogenic role in glioblastoma by functioning as a molecular sponge for microRNA-520f-3p

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x15982623243955 ◽

2020 ◽

Author(s):

Hengzhou Lin ◽

Dahui Zuo ◽

Jiabin He ◽

Tao Ji ◽

Jianzhong Wang ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Cell Counting ◽

Migration And Invasion ◽

Tumor Diameter ◽

Polymerase Chain ◽

Specificity Protein

The long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) plays anoncogenic role in hepatocellular carcinoma and triple negative breast cancerprogression. In this study, we investigated the expression and roles of WEE2-AS1 inglioblastoma (GBM). Furthermore, the molecular mechanisms behind the oncogenicactions of WEE2-AS1 in GBM cells were explored in detail. WEE2-AS1 expressionwas detected using quantitative real-time polymerase chain reaction. The roles ofWEE2-AS1 in GBM cells were evaluated by the Cell Counting Kit-8 assay, flowcytometric analysis, and Transwell cell migration and invasion assays, and tumorxenograft experiments. WEE2-AS1 expression was evidently enhanced in GBM tissuesand cell lines compared with their normal counterparts. An increased level of WEE2-AS1 was correlated with the average tumor diameter, Karnofsky Performance Scalescore, and shorter overall survival among GBM patients. Functionally, depleted WEE2-AS1 attenuated GBM cell proliferation, migration, and invasion in vitro, promoted cellapoptosis, and impaired tumor growth in vivo. Mechanistically, WEE2-AS1 functionedas a molecular sponge for microRNA-520f-3p (miR-520f-3p) and consequentlyincreased specificity protein 1 (SP1) expression in GBM cells. A series of recoveryexperiments revealed that the inhibition of miR-520f-3p and upregulation of SP1 couldpartially abrogate the influences of WEE2-AS1 downregulation on GBM cells. Inconclusion, WEE2-AS1 can adsorb miR-520f-3p to increase endogenous SP1expression, thereby facilitating the malignancy of GBM. Therefore, targeting theWEE2-AS1-miR-520f-3p-SP1 pathway might be a promising therapy for themanagement of GBM in the future.

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LncRNA DCST1-AS1 Promotes Endometrial Cancer Progression by Modulating the MiR-665/HOXB5 and MiR-873-5p/CADM1 Pathways

Frontiers in Oncology ◽

10.3389/fonc.2021.714652 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jie Wang ◽

Changjiang Lei ◽

Pingping Shi ◽

Huaixiang Teng ◽

Lixiang Lu ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Progression ◽

Noncoding Rna ◽

Migration And Invasion ◽

Potential Therapeutic Target ◽

Tumorigenesis And Progression ◽

Cell Adhesion Molecule 1

Dysregulation of long noncoding RNA (lncRNA) is implicated in the initiation and progression of various tumors, including endometrial cancer (EC). However, the mechanism of lncRNAs in EC tumorigenesis and progression remains largely unexplored. In this work, we identified a novel lncRNA DC-STAMP domain-containing 1-antisense 1 (DCST1-AS1), which is highly upregulated and correlated with poor survival in EC patients. Overexpression of DCST1-AS1 significantly enhanced EC cell proliferation, colony formation, migration, and invasion in vitro and promoted tumor growth of EC in vivo. Mechanistically, DCST1-AS1 mediated EC progression by inducing the expression of homeobox B5 (HOXB5) and cell adhesion molecule 1 (CADM1), via acting as a competing endogenous RNA for microRNA-665 (miR-665) and microRNA-873-5p (miR-873-5p), respectively. In addition, we found that the expression of miR-665 and miR-873-5p was significantly downregulated, while HOXB5 and CADM1 expression levels were increased in EC tissues. Taken together, our findings support the important role of DCST1-AS1 in EC progression, and DCST1-AS1 may be used as a prognostic biomarker as well as a potential therapeutic target for EC.

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