MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways

Pei, Tiemin; Meng, F.; Pan, Xiao; Han, Jianyong; Song, Ran; Lan, Yaliang; Wang, Yan; Junlin, Xue; Qingfu, Lang; Zhefeng, He; Li, Jian; Guo, Zihao; Liu, Guoxing; Sun, Bei; Zhao, Ming; Meng, Qingwei; Liang, Desen; Liu, Lianxin

doi:10.1016/j.jhep.2019.11.021

Cited by 76 publications

(56 citation statements)

References 29 publications

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“…Finally, we analyzed the downstream pathway of WTAP/HMBOX1 in osteosarcoma. PI3K/AKT pathway was reported to an important role in the progression of various cancers including osteosarcoma 58 . We found that PI3K/AKT pathway were evidently repressed by shWTAP, which was abolished by HMBOX1 knockdown.…”

Section: Discussionmentioning

confidence: 99%

WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner

Chen

Zhi³

et al. 2020

Cell Death Dis

100

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N 6-methyladenosine (m 6 A) regulators are involved in the progression of various cancers via regulating m 6 A modification. However, the potential role and mechanism of the m 6 A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M 6 A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m 6 A modification at the 3′UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m 6 A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.

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Section: Discussionmentioning

confidence: 99%

WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner

Chen

Zhi³

et al. 2020

Cell Death Dis

100

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“…The IHC staining was quantified as the H -score, which has been validated for many types of cancer 19 – 21 . The images were acquired using a imaging system (Pannoramic MIDI) under identical conditions.…”

Section: Methodsmentioning

confidence: 99%

LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness

Zhu

Yuan

et al. 2020

Cell Death Dis

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Resistance of chemotherapy is one of causes of recurrence and poor prognosis in patients with colorectal cancer (CRC). The role of differentially expressed long non-coding RNA (lncRNA) in 5-fluorouracil (5-Fu) resistance has not been fully elucidated. Here we observed that lncRNA NEAT1 was associated with 5-Fu resistance in CRC. Our Functional studies showed that NEAT1 promoted 5-Fu resistance in colorectal cells. In addition, A-TAC sequencing and chromatin immunoprecipitation (ChIP) showed that NEAT1 affected chromatin remodeling, increased the acetylation levels of histones, increased their enrichment at the promoters of ALDH1 and c-Myc, and promoted the expression of ALDH1 and c-Myc. Taken together, our study suggested that NEAT1 promoted 5-Fu resistance and cancer stemness by remodeling chromatin. Our finding provides a novel role of NEAT1 and may provide a new strategy for the treatment of CRC 5-Fu resistance.

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“…In addition, we found that the prognostic accuracy of this threegene signature was superior to that of BTD, COL12A1 and FER alone ( Figure 6E). In comparison with other known prognostic biomarkers such as MUC1 [20] and MCU13 [21], we found that this threegene signature provides distinctly higher accuracy in terms of prognosis prediction for iCCA patients.…”

Section: Discussionmentioning

confidence: 81%

Identification of a Three-gene Signature Acting as a Novel Prognostic Biomarker in Intrahepatic Cholangiocarcinoma Patients

Tang¹,

Hunag²,

Li³

et al. 2020

Preprint

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Background: Intrahepatic cholangiocarcinoma (iCCA) patients have poor outcomes due to the lack of biomarkers for the selection of treatment options. The present study was conducted to find biomarkers with independent prognostic vaule in iCCA patients. Methods: Gene transcriptome profiles of E-MTAB-6389, TCGA-CHOL and GSE26566 were obtained from ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, respectively. Bioinformatic analyses were performed to screen novel biomarkers for predicting the prognosis of iCCA patients. Using multivariate Cox regression analyses, a 3-gene signature (BTD-FER-COL12A1) with potential prognostic value was identified and validated in both a training cohort and two validation cohorts. Results: A total of 177 iCCA patients were included in this study. From the key gene modules significantly associated with liver cirrhosis and overall survival (OS) of iCCA patients, we identified 89 hub genes for functional analyses. Cox-regression analyses in both the training and validation cohort indicate that FER, COL12A1 and BTD were independent risk factors for iCCA patients. A 3-gene signature (BTD-FER-COL12A1) with independent prognostic value in iCCA patients was validated in the training cohort, as well as in two validation cohorts. In terms of predicting the prognosis of iCCA patients, the receiver operating characteristics (ROC) curves showed that this 3-gene signature had superior prediction power to BTD, FER, and COL12A1 alone, as well as known biomarkers (MUC1, MUC13) of iCCA. Immunohistochemical staining of samples from The Human Protein Atlas showed that FER and COL12A1 were positively expressed in iCCA tissue, although BTD was not, while none of these genes was detected in normal tissue. These findings were consistent with the expression status of BTD, FER and COL12A1 at the transcriptional level. In addition, we found that FER and COL12A1 were significantly associated with the degree of infiltration by tumor-infiltrating immune cells. Conclusion: We discovered a three-gene signature with independent prognostic value as a novel biomarker for prediction prognosis of iCCA patients. Our findings may help to find novel therapeutic targets for precision treatment of iCCA.

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MUC13 promotes intrahepatic cholangiocarcinoma progression via EGFR/PI3K/AKT pathways

Cited by 76 publications

References 29 publications

WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner

WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner

LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness

Identification of a Three-gene Signature Acting as a Novel Prognostic Biomarker in Intrahepatic Cholangiocarcinoma Patients

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