Tumor‐Specific Transcripts Are Frequently Expressed in Hepatocellular Carcinoma With Clinical Implication and Potential Function

Zheng, Qiuling; Zhao, Jingjing; Yu, Hui; Zong, Huajie; Zhao, Yiming; Li, Yan; Wang, Yu; Bao, Yichao; Li, Yuchen; Chen, Bing; Guo, Weijie; Wang, Yilin; Chen, Zhiao; Zhao, Yingjun; Wang, Lu; He, Xianghuo; Huang, Shenglin

doi:10.1002/hep.30805

Cited by 18 publications

(15 citation statements)

References 38 publications

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“…The aberrantly expressed lncRNAs, which act as diagnostic markers, prognostic indicators or predictors of therapeutic response, have been reported in various types of cancer including HCC 23 , 24 . For instance, the identification of tumor-specific transcripts (TSTs), which contain many noncoding RNAs and are detectable in extracellular vesicles from HCC patients' blood, may provide new insights into the development of HCC diagnosis 25 . Our previous studies have identified MCM3AP-AS1 and A1BG-AS1 as potential biomarkers for predicting the prognosis of HCC 7 , 11 .…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis

Xiao¹,

Liu

Zhao³

et al. 2020

Int. J. Biol. Sci.

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Hepatocellular carcinoma (HCC), one of the main causes of cancer-related deaths globally, is characterized by rapid growth and high invasiveness. Accumulating evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in the growth and metastasis of HCC. Recently, lncRNA LINC01123 has been found to contribute to cell proliferation and aerobic glycolysis in lung cancer. However, the function of LINC01123 in HCC, as well as the underlying mechanism of its action, remain unclear. Here, we found that the expression of LINC01123 was clearly upregulated in HCC tissues compared to nontumor tissues. Furthermore, expression of LINC01123 in HCC cells was significantly higher than in LO2 cells. Importantly, the upregulated level of LINC01123 was related to unfavorable clinical features and poor prognosis of HCC. Next, we demonstrated that LINC01123 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro . Depletion of LINC01123 inhibited HCC xenograft growth in vivo . Conversely, ectopic expression of LINC01123 facilitated HCC cell proliferation and invasion. Mechanistically, LINC01123 acted as a molecular sponge for miR-34a-5p in HCC cells. Tuftelin1 (TUFT1) was identified as the target gene of miR-34a-5p. LINC01123 positively regulated TUFT1 level by targeting of miR-34a-5p in HCC cells. Notably, TUFT1 restoration can abolish miR-34a-5p-induced inhibitory effects on HCC cell proliferation, migration and invasion. In conclusion, LINC01123 was overexpressed in HCC and accelerated cancer cell proliferation and invasion by regulating the miR-34a-5p/TUFT1 axis.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis

Xiao¹,

Liu

Zhao³

et al. 2020

Int. J. Biol. Sci.

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“…Next, we explore the potential molecular mechanism of up-regulated expression of MAPK4 in ALI. DNA methylation is commonly invoked as a mechanism for transcriptional repression [ 26 – 28 ], we wondered whether DNA demethylation of CpG island in MAPK4 promoter is contributed to the elevated expression of MAPK4 in ALI. Bioinformatics analysis indicated that there was a CpG island in the promoter of MAPK4 (Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

et al. 2020

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Background Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4−/− mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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“…Next, we explore the potential molecular mechanism of up-regulated expression of MAPK4 in ALI. DNA methylation is commonly invoked as a mechanism for transcriptional repression [26][27][28], we wondered whether DNA demethylation of CpG island in MAPK4 promoter is contributed to the elevated expression of MAPK4 in ALI. Bioinformatics analysis indicated that there was a CpG island in the promoter of MAPK4 ( Supplementary Fig.…”

Section: Nfkb1 and Nr3c1 Negatively Regulate The Expression Of Mapk4 mentioning

confidence: 99%

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

Mao

Zhou

Chen

et al. 2020

Preprint

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Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4 -/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

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Tumor‐Specific Transcripts Are Frequently Expressed in Hepatocellular Carcinoma With Clinical Implication and Potential Function

Cited by 18 publications

References 38 publications

Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis

Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury

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