Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

Peng, Haoran; Ishida, Masaharu; Li, Ling; Saito, Atsushi; Kamiya, Atsushi; Hamilton, James P.; Fu, Rongdang; Olaru, Alexandru; An, Fangmei; Popescu, Irinel; Iacob, Răzvan; Dima, Simona; Alexandrescu, Sorin; Grigorie, Răzvan; Năstase, Anca; Berindan‐Neagoe, Ioana; Tomuleasa, Ciprian; Graur, Florin; Zaharia, Florin; Torbenson, Michael; Mezey, Esteban; Lu, Min-qiang; Selaru, Florin M.

doi:10.18632/oncotarget.3290

Cited by 61 publications

(44 citation statements)

References 40 publications

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“…10 Other ncRNAs, such as long intergenic non-coding RNAs (lincRNAs) and the heterogeneous group of long non-coding RNAs (lncRNAs), have also been reported to be involved in human diseases. [11][12][13] LncRNA is most commonly defined as a non-protein-coding RNA molecule longer than 200 nucleotides. Increasing evidence has demonstrated that lncRNAs are involved in a wide range of biological processes, including differentiation, proliferation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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Section: Introductionmentioning

confidence: 99%

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

et al. 2017

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“…These findings suggest that lncRNA-ATB may serve as a potential antimetastatic target [67]. INTS6P1 is a pseudogene that exerts a tumor-suppressing function and upregulates its cognate gene INTS6 through competitive binding of oncogenic miR-17-5p in HCC [68]. …”

Section: The Function Of Cernas In Cancermentioning

confidence: 99%

The Emerging Function and Mechanism of ceRNAs in Cancer

et al. 2016

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Complex diseases such as cancer are often associated with aberrant gene expression at both the transcriptional and post-transcriptional level. In the past several years, competing endogenous RNAs (ceRNAs) have emerged as an important class of post-transcriptional regulators that alter gene expression through a microRNA-mediated mechanism. Recent studies in both solid tumors and hematopoietic malignancies showed that ceRNAs play significant roles in cancer pathogenesis by altering the expression of key tumorigenic or tumor suppressive genes. Characterizing the identity, function and mechanism of the ceRNAs will not only further our fundamental understanding of RNA-mediated cancer pathogenesis, but also may shed light on developing new RNA-based therapeutic strategies for treating cancer.

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“…Long non-coding RNAs (lncRNAs) also act as ceRNAs to facilitate protein-coding genes [20, 21]. miRNA-mediated gene regulation has been validated in HCC cells [22, 23], and several studies have confirmed the ceRNA mechanism in HCC cells [24, 25]. Thus, we need to consider ceRNAs which add a new layer of complexity to HCC biology.…”

Section: Introductionmentioning

confidence: 99%

PIK3C2A mRNA functions as a miR-124 sponge to facilitate CD151 expression and enhance malignancy of hepatocellular carcinoma cells

Liu

Wang

et al. 2016

Oncotarget

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Competing endogenous RNAs (ceRNAs) are RNA transcripts that can crosstalk with each other by competing for shared microRNAs (miRNAs) through miRNA response elements (MREs). Involved in ceRNA networks, the RNA transcripts may be in a balance, disruption of which could lead to tumorigenesis. Here we reveal a ceRNA interaction between PIK3C2A and CD151 mRNAs in hepatocellular carcinoma (HCC) cells. PIK3C2A is a candidate ceRNA of CD151 because mRNA 3′ untranslated regions (3′UTRs) of these two genes contain miR-124 binding sites. miR-124 is downregulated, while PIK3C2A and CD151 are upregulated in HCC cells compared with normal hepatocytes. Direct and negative regulation of PIK3C2A and CD151 by miR-124 was confirmed in HCC cells. miR-124 and the two potential ceRNAs are all recruited to the RNA-induced silencing complex (RISC). In HCC cell lines QGY- 7703 and SMMC-7721, and normal hepatic cell line HL-7702, miR-124 plays a tumor suppressor role by targeting PIK3C2A and CD151. The MREs within PIK3C2A 3′UTR can independently stimulate CD151 expression level by acting as miR-124 decoys. PIK3C2A MREs enhance HCC cell malignancy by absorbing endogenous miR-124 and activating CD151 in HCC cells. We conclude that PIK3C2A 3′UTR functions as a trans activator to stimulate CD151 by competing for miR-124 binding in HCC cells. The collaboration of PIK3C2A and CD151 through ceRNA mechanism may be implicated in HCC initiation and development.

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Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

Cited by 61 publications

References 40 publications

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

The Emerging Function and Mechanism of ceRNAs in Cancer

PIK3C2A mRNA functions as a miR-124 sponge to facilitate CD151 expression and enhance malignancy of hepatocellular carcinoma cells

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