circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma

Chen, Genwen; Shi, Yanting; Liu, Mengmeng; Sun, Jian‐Yong

doi:10.1038/s41419-017-0204-3

Cited by 243 publications

(198 citation statements)

References 39 publications

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“…circMTO1 suppresses HCC proliferation and invasion by sponging miR‐9 and upregulating the downstream p21 . circHIPK3 facilitates HCC progression through serving as a miR‐124 sponge and subsequently modulating AQP3 in HCC . Given the cytoplasmic location of circLARP4, we speculated that circLARP4 might function as a miRNA sponge to dampen HCC malignant phenotypes.…”

Section: Discussionmentioning

confidence: 99%

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

Chen

Zuo

et al. 2019

Cancer Science

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Circular RNAs (circRNAs), a novel class of non‐coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumors is yet to determined. Here, we investigated the role of circLARP4 in cellular senescence and cell proliferation in hepatocellular carcinoma (HCC). Downregulated circLARP4 level was observed in HCC tissues and cell lines. Low expression level of circLARP4 independently predicted poor survival outcome. Gain‐of‐function and loss‐of‐function assays demonstrated that circLARP4 suppressed HCC cell proliferation, mediated cell cycle arrest and induced senescence in vitro. Levels of p53 and p21, 2 key regulatory molecules in cellular senescence, were increased in circLARP4‐overexpressed HCC cells and decreased in circLARP4‐silenced HCC cells. In vivo experiments further confirmed the tumor‐suppressing activity of circLARP4. Further mechanistic studies showed that circLARP4 dampened HCC progression by sponging miR‐761, thereby promoting the expression level of RUNX3 and activating the downstream p53/p21 signaling. Our study revealed the role of circLARP4/miR‐761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC.

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Section: Discussionmentioning

confidence: 99%

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

Chen

Zuo

et al. 2019

Cancer Science

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“…Increased AQP3 expression was found in HCC and was negatively correlated with miR‐124 expression. AQP3 could be reduced by overexpressing miR‐124, thereby inhibiting the proliferation and migration of hepatoma . Another HCC‐related study demonstrated that miR‐124 could further inhibit the proliferation of HCC cells (SMMC‐7721) by regulating Baculoviral IAP Repeat Containing 3 (BIRC3) and controlling the NF‐kB pathway and migration.…”

Section: Mir‐124 and Hepatocellular Carcinomamentioning

confidence: 99%

MicroRNA‐124: An emerging therapeutic target in cancer

et al. 2019

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MicroRNAs (miRNAs) are noncoding single‐stranded RNAs, approximately 20‐24 nucleotides in length, known as powerful posttranscriptional regulators. miRNAs play important regulatory roles in cellular processes by changing messenger RNA expression and are widely involved in human diseases, including tumors. It has been reported in the literature that miRNAs have a precise role in cell proliferation, programmed cell death, differentiation, and expression of coding genes. MicroRNA‐124 (miR‐124) has reduced exparession in various human neoplasms and is believed to be related to the occurrence, development, and prognosis of malignant tumors. In our review, we focus on the specific molecular functions of miR‐124 and the downstream gene targets in major cancers, which provide preclinical evidence for the treatment of human cancer. Although some obstacles exist, miR‐124 is still attracting intensive research focus as a promising and effective anticancer weapon.

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“…Based on RNA‐sequence technology, Zheng et al discovered that circ HIPK3 (hsa_circ_0000284) is significantly upregulated in liver cancer compared with matched normal tissues and directly binds to miR‐124, thereby upregulating Interleukin 6 receptor (IL6R) and Homeobox protein DLX2 expression. Chen et al discovered that hsa_circ_0000284 promotes HCC proliferation and migration by directly binding to miR‐124, thereby upregulating aquaporin 3 (AQP3) expression. By sponging miR‐17‐3p and miR‐181b‐5p, hsa_circ_0001445 promotes the expression of metalloproteinase inhibitor 3 (TIMP3) and then inhibits the proliferation and migration of HCC cells .…”

Section: Circrnas and Hccmentioning

confidence: 99%

Circular RNAs in hepatocellular carcinoma: Functions and implications

Jiang

et al. 2018

Cancer Medicine

109

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At present, as hotspot members of the noncoding RNA network, circular RNAs (circRNAs) with distinct properties and diverse pathophysiological functions are being increasingly delineated. CircRNAs play roles at the epigenetic, transcriptional and posttranscriptional regulatory levels. Major studies have focused on their functions as efficient microRNA sponges. The validated number of endogenous circRNAs involved in hepatocellular carcinoma (HCC) continues to increase. Altered circRNA expression is associated with HCC occurrence, invasion, and metastasis. Moreover, the aberrant expression of circRNAs is also significantly related to HCC tumor stage, size, differentiation and metastasis. Because they are exceptionally stable, highly conserved and have tissue‐specific expression patterns, some circRNAs, including hsa_circ_0004018, hsa_circ_0003570, and hsa_circ_0005075, may be potential markers for the diagnosis of HCC. We herein summarize the current knowledge of HCC‐associated circRNAs and present their implications for carcinogenesis and their potential value as diagnostic and prognostic biomarkers. Finally, we discuss the future directions of studies on HCC‐associated circRNAs.

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circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma

Cited by 243 publications

References 39 publications

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

circLARP4 induces cellular senescence through regulating miR‐761/RUNX3/p53/p21 signaling in hepatocellular carcinoma

MicroRNA‐124: An emerging therapeutic target in cancer

Circular RNAs in hepatocellular carcinoma: Functions and implications

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