Long noncoding RNA PiHL regulates p53 protein stability through GRWD1/RPL11/MDM2 axis in colorectal cancer

Deng, Xuan; Li, Sihan; Kong, Fanyang; Ruan, Haoyu; Xu, Xiaowu; Zhang, Xinju; Wu, Zhiyuan; Zhang, Lin; Xü, Ying; Yuan, Hong; Peng, Haixia; Yang, Da; Guan, Ming

doi:10.7150/thno.36045

Cited by 48 publications

(38 citation statements)

References 50 publications

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“…These regulatory functions of lncRNAs influence the mRNA expression of the target genes, consequently modulating their protein expression levels. Moreover, lncRNAs are able to affect protein expression level independently, without influencing the mRNA expression level, by predominantly regulating mRNA translation and protein stability [14,15]. In the present study, we identified that the lncRNA RP11-284P20.2 interacts with c-met mRNA via complementary base pairing, and also found that RP11-284P20.2 binds to EIF3b protein with high affinity.…”

Section: Discussionsupporting

confidence: 52%

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

et al. 2020

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A newly identified lncRNA designated as RP11-284P20.2 has been identified to be up-regulated in hepatocellular carcinoma (HCC), but its role in HCC remain poorly understood. Quantitative PCR and immunocytochemical analysis were performed using the HCC tissues to identify the potential interaction partners of RP11-284P20.2. Moreover, RP11-284P20.2 was knocked down in HCC cell lines, HepG2 and SMMC7721, to investigate the influence of this lncRNA on cell growth properties. Additionally, RNA fluorescence in situ hybridization and immunofluorescence, RNA immunoprecipitation, and RNA pull-down assays were performed to determine the interaction of RP11-284P20.2 with c-met mRNA and eukaryotic translation initiation factor 3b (EIF3b). Silencing RP11-284P20.2 inhibited cell viability, migration, invasion, and colony formation, and increased apoptosis. Overexpression of c-met abolished these effects of RP11-284P20.2 in HCC cells. Histopathological examination showed that HCC tissues with high RP11-284P20.2 expression had higher c-met protein level than that in HCC tissues with low RP11-284P20.2 expression. However, there was no positive correlation between the expression levels of RP11-284P20.2 and c-met mRNA. RP11-284P20.2 knockdown led to a decease in c-met protein expression level, but did not affect the c-met mRNA expression level. These data suggest that RP11-284P20.2 regulates c-met protein expression level, which is independent of c-Met mRNA expression level. It was also confirmed that RP11-284P20.2 has high affinity toward both c-met mRNA and EIF3b protein, and hence RP11-284P20.2 probably recruits EIF3b protein to c-met mRNA and further facilitates its translation. RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

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Section: Discussionsupporting

confidence: 52%

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

et al. 2020

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“…Interestingly, a coimmunoprecipitation assay revealed that DJ-1 does not directly interact with p53 in CRC. An oncogene signaling pathway has been found to contribute to apoptosis by targeting MDM2 and indirectly activating the p53 pathway (36)(37). Therefore, the current study explored whether activation of the MDM2/ p53 pathway mediated the oncogenic effects of DJ-1 in CRC.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of DJ-1 enhances colorectal cancer cell proliferation through the cyclin-D1/MDM2-p53 signaling pathway

Zhu

Luo

Kang

et al. 2020

BST

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Emerging evidence indicates that DJ-1 is highly expressed in different cancers. It modulates cancer progression, including cell proliferation, cell apoptosis, invasion, and metastasis. However, its role in colorectal cancer (CRC) remains poorly defined. The current study noted increased DJ-1 expression in CRC tumor tissue and found that its expression was closely related to clinicalpathological features. Similarly, DJ-1 increased in CRC cells (SW480, HT-29, Caco-2, LoVo, HCT116, and SW620), and especially in SW480 and HCT116 cells. Functional analyses indicated that overexpression of DJ-1 promoted CRC cell invasion, migration, and proliferation in vitro and in vivo. Mechanistic studies indicated that DJ-1 increased in CRC cell lines, activated specific protein cyclin-D1, and modulated the MDM2/p53 signaling pathway by regulating the levels of the downstream factors Bax, Caspase-3, and Bcl-2, which are related to the cell cycle and apoptosis. Conversely, knockdown of DJ-1 upregulated p53 expression by disrupting the interaction between p53 and MDM2 and inhibiting CRC cell proliferation, revealing the pro-oncogenic mechanism of DJ-1 in CRC. In conclusion, the current findings provide compelling evidence that DJ-1 might be a promoter of CRC cell invasion, proliferation, and migration via the cyclin-D1/MDM2-p53 signaling pathway. Findings also suggest its potential role as a postoperative adjuvant therapy for patients with CRC.

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“…p53 is frequently inactivated or lowly expressed in human cancer, and it is able to directly bind to gene promoters to promote or inhibit gene expression ( Vousden and Prives, 2009 ). Currently, numerous lncRNAs are identified as the targets of p53, such as uc061hsf.1 ( Yao et al, 2020 ), PiHL ( Deng et al, 2020 ), and TRMP ( Yang et al, 2018 ). Herein, two p53 binding motifs on ST8SIA6-AS1 promoter were predicted using in silico analysis, and we performed ChIP and luciferase reporter assays and found that p53 could bind to the motif away from the transcription initiation site, inhibiting ST8SIA6-AS1 expression.…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p

Cao

Yang²,

et al. 2020

Front. Genet.

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Emerging evidence suggests that long non-coding RNA (lncRNA) plays a critical role in human disease progression. Recently, a novel lncRNA ST8SIA6-AS1 was shown as an important driver in various cancer types. Nevertheless, its contribution to lung adenocarcinoma (LUAD) remains undocumented. Herein, we found that ST8SIA6-AS1 was frequently overexpressed in LUAD cell lines, tissues, and plasma. Depletion of ST8SIA6-AS1 significantly inhibited LUAD cell proliferation and invasion in vitro and tumor growth in vivo. In term of mechanism, ST8SIA6-AS1 was transcriptionally repressed by tumor suppressor p53, and ST8SIA6-AS1 was mainly located in the cytoplasm and could abundantly sponge miR-125a-3p to increase nicotinamide N-methyltransferase (NNMT) expression, thereby facilitating LUAD malignant progression. Clinically, high ST8SIA6-AS1 was positively correlated with larger tumor size, lymph node metastasis, and later TNM stage. Moreover, ST8SIA6-AS1 was identified as an excellent indicator for MM diagnosis and prognosis. Collectively, our data demonstrate that ST8SIA6-AS1 is a carcinogenic lncRNA in LUAD, and targeting the axis of ST8SIA6-AS1/miR-125a-3p/NNMT may be a promising treatment for LUAD patients.

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Long noncoding RNA PiHL regulates p53 protein stability through GRWD1/RPL11/MDM2 axis in colorectal cancer

Cited by 48 publications

References 50 publications

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

Overexpression of DJ-1 enhances colorectal cancer cell proliferation through the cyclin-D1/MDM2-p53 signaling pathway

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p

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