Long non-coding RNA 657 suppresses hepatocellular carcinoma cell growth by acting as a molecular sponge of miR-106a-5p to regulate PTEN expression

Hu, Bingren; Cai, Huajie; Zheng, Rujie; Yang, Shouzhang; Zhou, Zhenxu; Tu, Jinfu

doi:10.1016/j.biocel.2017.09.008

Cited by 58 publications

(41 citation statements)

References 21 publications

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“…So far, lncRNAs have been demonstrated to regulate gene expression at both the transcriptional and posttranscriptional levels ( Chen, 2016 ). It has been reported that the lncRNAs have been shown to play significant effects on several liver diseases, such as hepatic fibrosis and hepatocellular carcinoma ( Bian et al, 2017 ; Hu et al, 2017 ). Maternally expressed gene 3 (MEG3) is an lncRNA with a length of ∼1.6 kb nucleotides and is reciprocally imprinted with the paternally expressed gene DLK1 constituting an imprinting domain on human chromosome 14q32, with its homolog of mouse MEG3 on the distal region of mouse chromosome 12 ( Miyoshi et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5

Wang

Shen

et al. 2018

Front. Pharmacol.

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Ethanol (EtOH)-induced hepatic injury, characterized by hepatic steatosis with apoptosis, causes heavy health burden personally and socially. Long non-coding RNAs (lncRNAs) have been implicated in liver diseases. However, the role of lncRNA maternally expressed gene 3 (MEG3) in EtOH-induced hepatic injury remains unknown. The aim of present study was to assess the function of MEG3 and its functional interaction with miR-let-7c-5p in EtOH-induced hepatic injury. Here, we observed that MEG3 and NLRC5 expression was increased and miR-let-7c-5p expression decreased in EtOH-fed mice and EtOH-induced AML-12 cells. Knockdown of MEG3 contributed to attenuation of EtOH-induced steatosis and apoptosis in AML-12 cells. Also, expression level of MEG3 negatively correlated with miR-let-7c-5p expression and positively correlated with NLRC5 expression. In contrary to MEG3, miR-let-7c-5p overexpression attenuated EtOH-induced steatosis and apoptosis, as well as suppressed EtOH-induced increase in NLRC5 expression. By luciferase reporter assay, we concluded that miR-let-7c-5p directly binds to NLRC5 3′-UTR, thereby negatively regulates NLRC5 expression. Our data suggested that lncRNA MEG3 functions as a competing endogenous RNA for miR-let-7c-5p to regulate NLRC5 expression in EtOH-induced hepatic injury.

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Section: Introductionmentioning

confidence: 99%

The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5

Wang

Shen

et al. 2018

Front. Pharmacol.

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“…As an example, in HCC, the lncRNA TUG1 was shown to regulate the Hedgehog pathway by targeting miR-132 [ 19 ]. The LncRNA 657 was demonstrated to suppress HCC cell growth by sponging miR-106a-5p [ 20 ] and MALAT1 promotes HCC progression by down-regulating miR-146b-5p through its sponge function, thereby promoting cancer growth and metastasis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNAs as novel players in hepatocellular carcinoma recurrence

et al. 2018

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Long non-coding RNAs (lncRNAs) are ncRNAs more than 200 nucleotides long that participate to a wide range of biological functions. However, their role in cancer is poorly known. By using an NGS-based approach we analyzed the intragenic and poliA-lncRNAs in hepatocellular carcinoma (HCC) and we assayed the relationships between their deregulated expression and clinical-pathological characteristics. The expression profile of lncRNAs was studied in a discovery series of 28 HCC and matched cirrhosis and was validated in an independent cohort of 32 HCC patients both in tissue and serum. The correlation between lncRNA expression and clinical-pathological variables, EMT markers and putative sponged microRNAs level were investigated. Functional experiments were performed in HCC-derived cell lines to clarify the role of selected lncRNAs in HCC. A panel of deregulated lncRNAs differentiated HCC from cirrhotic tissue. CASC9 and LUCAT1 were up-regulated in a subset of HCC-derived cell lines and in half of HCCs which displayed a lower recurrence after surgery. LUCAT1 and CASC9 silencing increased cell motility and invasion capability in HCC cells and influenced the EMT phenotype. LUCAT1 was demonstrated to directly sponge the onco-miR-181d-5p. Both LUCAT1 and CASC9 were secreted in exosomes, and higher circulating CASC9 levels were associated with tumor size and HCC recurrence after surgery, suggesting its potential usage as putative non-invasive prognostic biomarker of recurrence.

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“…NORAD is elevated in HCV-infected hepatocytes. Aberrant expression of NORAD has been reported in several cancers, including esophageal, breast, colorectal, and pancreatic cancers (25)(26)(27)(28). On the other hand, differential expression of NORAD has been reported in HCC, although higher expression of NORAD was correlated with poor survival (25).…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant expression of NORAD has been reported in several cancers, including esophageal, breast, colorectal, and pancreatic cancers (25)(26)(27)(28). On the other hand, differential expression of NORAD has been reported in HCC, although higher expression of NORAD was correlated with poor survival (25). Abnormal expression of the Pumilio 1 gene is associated with chromosomal aberration and cancer, neurological disorder, and cardiovascular disease (29,30).…”

Section: Discussionmentioning

confidence: 99%

Association between MicroRNA-373 and Long Noncoding RNA NORAD in Hepatitis C Virus-Infected Hepatocytes Impairs Wee1 Expression for Growth Promotion

Sur

Sasaki

Devhare

et al. 2018

J Virol

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Chronic hepatitis C virus (HCV) infection may lead to end-stage liver disease, including hepatocellular carcinoma (HCC). We have shown previously that microRNA-373 (miR-373) is upregulated in HCV-infected human liver biopsy specimens. To gain insight into the role of miR-373 in HCV-mediated pathogenesis, we investigated its interacting partner for hepatocyte growth regulation. Transcriptome sequencing (RNA-seq) data revealed that Wee1 is associated with miR-373 and is a direct target. Interestingly, higher expression of Wee1 was noted in HCV-infected hepatocytes than in uninfected hepatocytes, suggesting that other factors may block miR-373-mediated Wee1 inhibition. We subsequently found an association between the long noncoding RNA NORAD (LINC00657) and miR-373, and we demonstrated that NORAD binds to miR-373 and Wee1 independently. However, the high level of Wee1 expression in HCV-infected hepatocytes suggested that miR-373 forms a complex with NORAD. Depletion of miR-373 or the inhibitor Wee1 reduces the growth of Huh7.5 cells harboring the HCV genome as well as reducing Wee1 expression. Taken together, our data demonstrate a novel mechanism of hepatocyte growth promotion during HCV infection involving a miR-373-NORAD-Wee1 axis, which may be a target for future therapy against HCV-associated HCC. The mechanism of HCV-mediated liver pathogenesis is poorly understood. In this study, we observed that HCV infection upregulates miR-373 and Wee1, a pivotal player in the G checkpoint in the cell cycle, although Wee1 is a direct target for miR-373. Subsequent investigation demonstrated that miR-373 forms a complex with the long noncoding RNA NORAD, resulting in the release of their common target, Wee1, in HCV-infected cells, which, in turn, favors uncontrolled cell growth. Our study suggested a previously unknown mechanism for hepatocyte growth promotion following HCV infection, and this pathway can be targeted for future therapy against HCV-mediated liver pathogenesis.

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Long non-coding RNA 657 suppresses hepatocellular carcinoma cell growth by acting as a molecular sponge of miR-106a-5p to regulate PTEN expression

Cited by 58 publications

References 21 publications

The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5

The Long Non-coding RNA MEG3/miR-let-7c-5p Axis Regulates Ethanol-Induced Hepatic Steatosis and Apoptosis by Targeting NLRC5

LncRNAs as novel players in hepatocellular carcinoma recurrence

Association between MicroRNA-373 and Long Noncoding RNA NORAD in Hepatitis C Virus-Infected Hepatocytes Impairs Wee1 Expression for Growth Promotion

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