Long Non-coding RNA URHC Regulates Cell Proliferation and Apoptosis via ZAK through the ERK/MAPK Signaling Pathway in Hepatocellular Carcinoma

Xu, Weihua; Zhang, Jianbin; Dang, Zheng; Li, Xiao; Zhou, Ti; Liu, Jie; Wang, Desheng; Song, Wenjie; Dou, Kefeng

doi:10.7150/ijbs.8232

Cited by 103 publications

(90 citation statements)

References 50 publications

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“…LncRNAs have been reported to be important in cell apoptosis, particularly in the escape of cancer cells from apoptosis (20)(21)(22). To determine the impact of TRIM52-AS1 on RCC cell apoptosis, flow cytometry was performed to detect the rate of apoptosis in the cells.…”

Section: Downregulation Of Trim52-as1 Promotes Rcc Cell Apoptosis In mentioning

confidence: 99%

Downregulation of long non-coding RNA TRIM52-AS1 functions as a tumor suppressor in renal cell carcinoma

Liu

Yan

Xia

et al. 2016

Molecular Medicine Reports

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Abstract. Long non-coding RNAs (lncRNAs) are important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation and survival. Alterations in the function of lncRNAs promote tumor formation, progression and metastasis. The purpose of the present study was to identify novel tumor suppressor lncRNAs, and elucidate their physiological function and mechanism in renal cell carcinoma (RCC). The results of the present study revealed that the expression of the lncRNA, TRIM52-AS1, was downregulated in RCC, which was demonstrated using reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, the effects of TRIM52-AS1 on proliferation, cell migration and apoptosis were analyzed using a wound scratch assay, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometric analysis, respectively. The overexpression of TRIM52-AS1 using a synthesized vector significantly suppressed cell migration and proliferation, and induced apoptosis of the RCC cells in vitro, and interference of its expression led to the opposite effects. The present study was the first, to the best of our knowledge, to demonstrate that TRIM52-AS1 functions as a tumor suppressor in RCC. Further investigation is required to elucidate the molecular mechanisms underlying the effects of TRIM52-AS1 in the development of RCC.

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Section: Downregulation Of Trim52-as1 Promotes Rcc Cell Apoptosis In mentioning

confidence: 99%

Downregulation of long non-coding RNA TRIM52-AS1 functions as a tumor suppressor in renal cell carcinoma

Liu

Yan

Xia

et al. 2016

Molecular Medicine Reports

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“…High level of up-regulated in hepatocellular carcinoma (URHC) expression is significantly associated with tumor size, tumor number and shorter overall survival after surgery [81] . URHC can regulate cell proliferation and apoptosis by repressing ZAK expression.…”

Section: Up-regulated In Hepatocellular Carcinomamentioning

confidence: 99%

“…ZAK, also known as MLK-like MAP triple kinase-α or ZAK-α, belongs to the mixed lineage kinase family and functions as a tumor-suppressor gene in HCC [110] . Inactivation of the ERK/MAPK pathway is required for the increase in HCC growth, which is induced by URHC-ZAK regulation [81] . However, only microarray analysis was done, which limited its conviction.…”

Section: Up-regulated In Hepatocellular Carcinomamentioning

confidence: 99%

Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism

Liu

Tang

Huang

et al. 2015

WJH

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Hepatocellular carcinoma (HCC) is the predominant subject of liver malignancies which arouse global concern. Advanced studies have found that long noncoding RNAs (lncRNAs) are differentially expressed in HCC and implicate they may play distinct roles in the pathogenesis and metastasis of HCC. However, the underlying mechanisms remain largely unclear. In this review, we summarized the functions and mechanisms of those known aberrantly expressed lncRNAs identified in human HCC tissues. We hope to enlighten more comprehensive researches on the detailed mechanisms of lncRNAs and their application in clinic, such as being used as diagnostic and prognostic biomarkers and the targets for potential therapy. Although studies on lncRNAs in HCC are still deficient, an improved understanding of the roles played by lncRNAs in HCC will lead to a much more effective utilization of those lncRNAs as novel candidates in early detection, diagnosis, prevention and treatment of HCC.

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“…The mRNA expression level was evaluated using evaluated threshold cycle (Cq) values. The Cq values were normalized to the expression levels of GAPDH and the relative amount of mRNA specific to each of the target genes was determined using the 2 -ΔΔCq method (18)(19)(20)(21)(22). qPCR was performed with the BIO-RAD CFK96 TM Real-Time System (Bio-Rad Laboratories, Inc., Hercules, CA, USA).…”

Section: Total Rna Extraction and Reverse Transcription-quantitative mentioning

confidence: 99%

“…The crucial etiological factors involved in the development of HCC include infection with hepatitis virus, the structural or functional mutation of oncogenes and tumor suppressor genes (19)(20)(21). Long non-coding RNA URHC regulates cell proliferation and apoptosis by zinc-activated channels via the extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling pathway in HCC (22), and microRNA-24 may modify aflatoxin B1-related HCC prognosis and tumorigenesis (23). Therefore, it is necessary to further the research in this area in order to improve the diagnosis and treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Sperm-associated antigen 9 is upregulated in hepatocellular carcinoma tissue and enhances QGY cell proliferation and invasion inï¿½vitro

Ren

Zou

et al. 2017

Oncol Lett

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Abstract.The incidence and mortality rates of hepatocellular carcinoma (HCC) are higher in China compared with in other countries. Further research is required in order to improve the diagnosis and treatment of HCC. Sperm-associated antigen 9 (SPAG9) protein has been revealed to serve an important function in cancer progression; however, the underlying mechanisms remain to be elucidated. The present study investigated the expression level of SPAG9 in HCC tissues using quantitative-polymerase chain reaction, immunohistochemistry and western blotting, and the results demonstrated that SPAG9 was overexpressed in HCC tissues compared with the adjacent non-cancerous tissues. To explore the potential mechanisms underlying SPAG9 in HCC, the effect of SPAG9 on cell proliferation, cell cycle, migration and invasion capacities were investigated in the QGY HCC cell line by RNA interference. It was revealed that inhibition of SPAG9 mRNA in QGY cells significantly inhibited the expression level of SPAG9 compared with the control. Depletion of SPAG9 expression decreased cell proliferation (P<0.01) and increased the percentage of cells in the G 1 /G 2 cell cycle phase. The percentage of cells in the S phase was decreased, and cell migration and invasion capabilities in vitro were reduced (P<0.01). In summary, the results of the present study suggested that SPAG9 was upregulated in HCC and may serve an important function in cancer cell proliferation, differentiation and invasion. Whether SPAG9 is a potential diagnostic marker and therapeutic target of human HCC requires additional study. IntroductionSperm-associated antigen 9 (SPAG9) has characteristics of a scaffold protein and is involved in the c-Jun N-terminal kinase JNK signaling pathway, binding to JNK, which suggests that it is involved in physiological processes, including apoptosis, survival, proliferation and tumorigenesis (1,2). SPAG9 is a member of the cancer/testis antigen family expressed from a single copy gene located on human chromosome 17q21. Proteins in the cancer/testis antigen family are overexpressed in a variety of types of cancer (3,4). SPAG9 is also expressed in a variety of tumors (5-9). SPAG9 has been proposed as a novel biomarker for early diagnosis of multiple human tumors, including ovarian, cervical and breast cancers (10-12). Certain studies have revealed that small interfering RNA inhibits expression of SPAG9 and inhibits the growth of various types of tumor cells (13,14). SPAG9 protein has been demonstrated to be involved in cancer progression; however, the underlying mechanisms remain unknown (15,16).Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally and is the third most common cause of cancer-associated mortality (17). The incidence of HCC is higher in South East Asia and Africa compared with other regions of the world (18). The crucial etiological factors involved in the development of HCC include infection with hepatitis virus, the structural or functional mutation of oncogenes and tumor suppressor genes (19-21...

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Long Non-coding RNA URHC Regulates Cell Proliferation and Apoptosis via ZAK through the ERK/MAPK Signaling Pathway in Hepatocellular Carcinoma

Cited by 103 publications

References 50 publications

Downregulation of long non-coding RNA TRIM52-AS1 functions as a tumor suppressor in renal cell carcinoma

Downregulation of long non-coding RNA TRIM52-AS1 functions as a tumor suppressor in renal cell carcinoma

Long noncoding RNAs in hepatocellular carcinoma: Novel insights into their mechanism

Sperm-associated antigen 9 is upregulated in hepatocellular carcinoma tissue and enhances QGY cell proliferation and invasion inï¿½vitro

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