The long noncoding RNA lncPARP1 contributes to progression of hepatocellular carcinoma through up-regulation of PARP1

Hepatocellular carcinoma (HCC) accounts for a large proportion of cancer-associated mortality worldwide. The functional impact of long noncoding RNAs (lncRNAs) in human cancer is not fully understood. Here, we identified a novel oncogenic lncRNA termed as lncPARP1, which was significantly up-regulated in HCC. Increase in lncPARP1 expression was associated with age, α-fetoprotein (AFP) levels, tumor size, recurrence, and poor prognosis of HCC patients. Loss-of-function approaches showed that knockdown of lncPARP1 inhibited proliferation, migration, and invasion, while induced apoptosis in HCC cells. Moreover, mechanistic investigation demonstrated that PARP1 was an underlying target of lncPARP1 in HCC. In summary, we provide the first evidence that lncPARP1 exerts an oncogene to promote HCC development and progression, at least in part, by affecting poly (ADP-ribose) (PAR) polymerase 1 (PARP1) expression.

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Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair

Cancers ◽

10.3390/cancers10090320 ◽

2018 ◽

Vol 10 (9) ◽

pp. 320 ◽

Cited By ~ 10

Author(s):

Chin-Chuan Chen ◽

Chi-Yuan Chen ◽

Shu-Huei Wang ◽

Chau-Ting Yeh ◽

Shih-Chi Su ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Repair ◽

Noncoding Rna ◽

Migration And Invasion ◽

Tumor Growth Inhibition ◽

Loss Of Function ◽

Repair Capacity ◽

Dna Repair Capacity ◽

Repair Mechanisms ◽

Hcc Cells

DNA repair systems are abnormally active in most hepatocellular carcinoma (HCC) cells due to accumulated mutations, resulting in elevated DNA repair capacity and resistance to chemotherapy and radiotherapy. Thus, targeting DNA repair mechanisms is a common treatment approach in HCC to sensitize cancer cells to DNA damage. In this study, we examined the anti-HCC effects of melatonin and elucidated the regulatory mechanisms. The results of functional assays showed that in addition to inhibiting the proliferation, migration, and invasion abilities of HCC cells, melatonin suppressed their DNA repair capacity, thereby promoting the cytotoxicity of chemotherapy and radiotherapy. Whole-transcriptome and gain- and loss-of-function analyses revealed that melatonin induces expression of the long noncoding RNA RAD51-AS1, which binds to RAD51 mRNA to inhibit its translation, effectively decreasing the DNA repair capacity of HCC cells and increasing their sensitivity to chemotherapy and radiotherapy. Animal models further demonstrated that a combination of melatonin and the chemotherapeutic agent etoposide (VP16) can significantly enhance tumor growth inhibition compared with monotherapy. Our results show that melatonin is a potential adjuvant treatment for chemotherapy and radiotherapy in HCC.

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Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

Cancer Cell International ◽

10.1186/s12935-019-1093-6 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 9

Author(s):

Qun Dai ◽

Jingyi Deng ◽

Jinrong Zhou ◽

Zhuhong Wang ◽

Xiao-feng Yuan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Progression ◽

Noncoding Rna ◽

Critical Role ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Marked Rise ◽

Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

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Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

Clinical & Translational Oncology ◽

10.1007/s12094-019-02223-7 ◽

2019 ◽

Vol 22 (3) ◽

pp. 302-310 ◽

Cited By ~ 5

Author(s):

Q. Y. Li ◽

K. Yang ◽

F. G. Liu ◽

X. G. Sun ◽

L. Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Progression ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Cancer Susceptibility ◽

Vital Role ◽

Migration And Invasion ◽

Tumor Tissues ◽

Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

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Long noncoding LINC00238 restrains Hepatocellular Carcinoma Malignant Phenotype via Sponging miR-522

10.21203/rs.3.rs-531043/v1 ◽

2021 ◽

Author(s):

Honggang Qian ◽

Qiong Wu ◽

Jian-Hui Wu ◽

Xiu-Yun Tian ◽

Wei Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Suppressor ◽

Cell Viability ◽

Noncoding Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Loss Of Function ◽

Malignant Phenotype ◽

Migration Ability ◽

Downstream Targets

Abstract Background: Long noncoding RNA (lncRNA) Can regulates tumor malignant phenotype either as a tumor suppressor or an oncogene. In hepatocellular carcinoma (HCC), the clinical significance and underlying mechanism of LINC00238 function remain undefined. Methods: Down-regulated expression levels of noncoding RNAs were screened from TCGA LIHC dataset through GEPIA software. The expression of RNAs were determined by qRT-PCR. Molecular clone was performed to over-expression and knockdown of LINC00238 expression. The levels of proteins were evaluated via Western blot. The cell viability, clone formation and migration ability were assessed by CCK-8, plate clone formation and Transwell assays. RNA pull down and Luciferase reporter assays were applied to detect the interplays between LINC00992 and miR-3935.Results: LINC00238 was identified as a significant downregulated both in TCGA and in our cohort, and its low expression was significantly correlated with bigger tumor size, early recurrence and poor survival of patients with HCC after surgery. Through the results of gain and loss of function experiments, LINC00238 was confirmed as a tumor suppressor， which could decrease not only cell viability, migration and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down showed that LINC00238 sponged mir-522, and then, released the inhibition effects on two downstream targets, SFRP2 and DKK1.Conclusions: We identified LINC00238 as a tumor suppressor by sponging miR-522 followed by release silencing of downstream targets, suggesting that LINC00238 has a key role in restraining the malignant phenotype of HCC cells and providing a novel perspective on lncRNAs in HCC progression.

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Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers12051193 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1193 ◽

Cited By ~ 1

Author(s):

Yeonhwa Song ◽

Sanghwa Kim ◽

Hyeryon Lee ◽

Joo Hwan No ◽

Hyung Chul Ryu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Human Cancer ◽

Point Mutations ◽

Cd133 Expression ◽

Control Tumor ◽

Induced Apoptosis ◽

Tumor Maintenance ◽

Hcc Cells

Hepatocellular carcinoma (HCC) is a highly malignant human cancer that has increasing mortality rates worldwide. Because CD133+ cells control tumor maintenance and progression, compounds that target CD133+ cancer cells could be effective in combating HCC. We found that the administration of chromenopyrimidinone (CPO) significantly decreased spheroid formation and the number of CD133+ cells in mixed HCC cell populations. CPO not only significantly inhibited cell proliferation in HCC cells exhibiting different CD133 expression levels, but also effectively induced apoptosis and increased the expression of LC3-II in HCC cells. CPO also exhibits in vivo therapeutic efficiency in HCC. Specifically, CPO suppressed the expression of CD133 by altering the subcellular localization of CD133 from the membrane to lysosomes in CD133+ HCC cells. Moreover, CPO treatment induced point mutations in the ADRB1, APOB, EGR2, and UBE2C genes and inhibited the expression of these proteins in HCC and the expression of UBE2C is particularly controlled by CD133 expression among those four proteins in HCC. Our results suggested that CPO may suppress stemness and malignancies in vivo and in vitro by decreasing CD133 and UBE2C expression in CD133+ HCC. Our study provides evidence that CPO could act as a novel therapeutic agent for the effective treatment of CD133+ HCC.

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LncRNA AFAP1-AS1 is a prognostic biomarker and serves as oncogenic role in retinoblastoma

Bioscience Reports ◽

10.1042/bsr20180384 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 14

Author(s):

Fengqin Hao ◽

Yanan Mou ◽

Laixia Zhang ◽

Shuna Wang ◽

Yang Yang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Lines ◽

Noncoding Rna ◽

Human Cancer ◽

Migration And Invasion ◽

Loss Of Function ◽

Retinoblastoma Cell ◽

Choroidal Invasion

The actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been found to serve as an oncogenic long noncoding RNA (lncRNA) in most types of human cancer. The role of AFAP1-AS1 in retinoblastoma remains unknown. The purpose of the present study is to explore the clinical significance and biological function of AFAP1-AS1 in retinoblastoma. Levels of AFAP1-AS1 expression were measured in retinoblastoma tissues and cell lines. Loss-of-function study was performed to observe the effects of AFAP1-AS1 on retinoblastoma cell proliferation, cell cycle, migration, and invasion. In our results, AFAP1-AS1 expression was elevated in retinoblastoma tissues and cell lines, and associated with tumor size, choroidal invasion, and optic nerve invasion. Moreover, high expression of AFAP1-AS1 was an independent unfavorable prognostic factor in retinoblastoma patients. The experiment in vitro suggested down-regulation of AFAP1-AS1 inhibited retinoblastoma cell proliferation, migration and invasion, and blocked cell cycle. In conclusion, AFAP1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

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Kinesin family member 2C promotes hepatocellular carcinoma growth and metastasis via activating MEK/ERK pathway

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab154 ◽

2021 ◽

Author(s):

Qian Ding ◽

Caihua Jiang ◽

Yajing Zhou ◽

Jianping Duan ◽

Jianming Lai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Family Member ◽

Poor Prognosis ◽

Migration And Invasion ◽

Erk Pathway ◽

High Level ◽

The Impact ◽

Kinesin Family ◽

Hcc Cells

ABSTRACT The current work was intended to explore the function and mechanism of Kinesin family member 2C (KIF2C) in hepatocellular carcinoma (HCC). In this study, KIF2C expression was at a high level in HCC and indicated poor prognosis. Silencing KIF2C significantly suppressed the proliferation, migration and invasion in HCC cells. Furthermore, silencing KIF2C markedly decreased the expression of Snail, Vimentin, p-MEK and p-ERK, but increased E-cadherin expression in HCC cells. Moreover, we also found that MEK/ERK inhibitor U0126 could enhance the impact on cell proliferation, migration and invasion induced by silencing KIF2C in HCC. On the contrary, MEK/ERK activator PAF could weaken the impact induced by silencing KIF2C in HCC. Thus, our findings indicate that KIF2C can promote the proliferation, migration and invasion by activating MEK/ERK pathway in HCC.

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Long Noncoding RNA KIAA0125 Potentiates Cell Migration and Invasion in Gallbladder Cancer

BioMed Research International ◽

10.1155/2015/108458 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Wenjie Lv ◽

Lei Wang ◽

Jianhua Lu ◽

Jiasheng Mu ◽

Yingbin Liu ◽

...

Keyword(s):

Cell Migration ◽

Gallbladder Cancer ◽

Noncoding Rna ◽

Poor Prognosis ◽

Noncoding Rnas ◽

Migration And Invasion ◽

Potential Therapeutic Target ◽

Cell Migration And Invasion ◽

Underlying Mechanisms ◽

Insight Into

Gallbladder cancer (GBC) is one of the mostly aggressive diseases with poor prognosis due to the lack of severe symptoms. To date, little is known about the potential roles and underlying mechanisms of long noncoding RNAs (lncRNAs) in GBC initiation and progression. Thus, it provides us with a novel insight into the contribution of lncRNAs to GBC development. Remarkably, we found the differential expression of a lncRNA, namely, KIAA0125, in a pair of GBC cell sublines which possess different metastatic potentials. Then the effects of KIAA0125 on GBC cell migration, invasion, and epithelial-mesenchymal transitions (EMT) were investigated by using a lentivirus-mediated RNA interference (RNAi) system. Notably, cell migration and invasion were strongly inhibited by KIAA0125 suppression. Moreover, the expression ofβ-Catenin was increased and the expression of Vimentin was decreased in GBC-SD/M cells after KIAA0125 knockdown. Thus, our findings suggested that KIAA0125 promoted the migration and invasion of GBC cells and could serve as a potential therapeutic target in advanced GBC.

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miR-186 Represses Proliferation, Migration, Invasion, and EMT of Hepatocellular Carcinoma via Directly Targeting CDK6

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x15954139263808 ◽

2020 ◽

Vol 28 (5) ◽

pp. 509-518

Author(s):

Junfeng Lu ◽

Zhongsong Zhao ◽

Yanhong Ma

Keyword(s):

Hepatocellular Carcinoma ◽

Vascular Invasion ◽

Poor Prognosis ◽

Untranslated Regions ◽

Migration And Invasion ◽

Synergic Effect ◽

Cyclin Dependent Kinase ◽

Biological Functions ◽

Inhibitory Effects ◽

Hcc Cells

The present study aimed to investigate the effect of miR-186 on proliferation, migration, invasion, and epithelialmesenchymal transition (EMT) of hepatocellular carcinoma (HCC). In this work, miR-186 was downregulated in HCC tissues and cells, and low miR-186 level helped predict the occurrence of vascular invasion and poor prognosis in patients with HCC. miR-186 overexpression inhibited cell proliferation and tumor growth in nude mice, repressed migration and invasion abilities, and enhanced apoptosis in HCC cells. miR-186 also retarded progression of EMT. miR-186 directly bound to the 3-untranslated regions of cyclin-dependent kinase 6 (CDK6) to inhibit its expression. Overexpression of CDK6 markedly reversed inhibitory effects of miR-186 on proliferation, apoptosis, migration, and invasion of HCC cells. Conversely, inhibition of CDK6 exerted synergic effect on the biological functions of miR-186. In conclusion, miR-186 represses proliferation, migration, invasion, and EMT, and induces apoptosis through targeting CDK6 in HCC, which may provide a new therapeutic target for HCC.

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The PU.1-Regulated Long Noncoding RNA Lnc-MC Controls Human Monocyte/Macrophage Differentiation through Interaction with MicroRNA-199a-5p

Molecular and Cellular Biology ◽

10.1128/mcb.00429-15 ◽

2015 ◽

pp. MCB.00429-15 ◽

Cited By ~ 20

Author(s):

Ming-Tai Chen ◽

Hai-Shuang Lin ◽

Chao Shen ◽

Yan-Ni Ma ◽

Fang Wang ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Noncoding Rnas ◽

Human Monocyte ◽

Regulation Mechanism ◽

Loss Of Function ◽

Macrophage Differentiation ◽

Hematopoietic Stem ◽

Mechanistic Investigation ◽

Repressive Effect

Long noncoding RNAs (lncRNAs) are emerging as important regulators in mammalian development, but little is known about their roles in monocyte/macrophage differentiation. Here we identified a long noncoding RNA MonoCyte (lnc-MC), which exhibits increased expression during monocyte/macrophage differentiation of THP-1 and HL-60 cells as well as CD34+hematopoietic stem/progenitor cells (HSPCs), and is transcriptionally activated by PU.1. Gain and loss of function assays demonstrate that lnc-MC promotes monocyte/macrophage differentiation of THP-1 cells and CD34+HSPCs. Mechanistic investigation reveals that lnc-MC acts as a competing endogenous RNA to sequester miR-199a-5p and alleviate repression on activin A receptor type 1B (ACVR1B) expression, an important regulator of monocyte/macrophage differentiation. We also noted repressive effect of miR-199a-5p on lnc-MC expression and function, but PU.1-dominant down-regulation of miR-199a-5p results in its adverse position in the reciprocal regulation between miR-199a-5p and lnc-MC. Altogether, our work uncovers that PU.1-regulated two noncoding RNAs, lnc-MC and miR-199a-5p, have opposing roles in monocyte/macrophage differentiation and during the differentiation lnc-MC further enforces PU.1's role to facilitate the process by sponging miR-199a-5p and releasing ACVR1B expression, which confers a novel regulation mechanism composed of PU.1, lnc-MC, miR-199a-5p and ACVR1B in the monocyte/macrophage differentiation.

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