General Information of the Disease (ID: M6ADIS0053)
Name
Malignant mixed epithelial mesenchymal tumour
ICD
ICD-11: 2B5D
Full List of Target Gene(s) of This m6A-centered Disease Response
Autophagy protein 5 (ATG5)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of Autophagy protein 5 (ATG5) and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Autophagy-related protein 101 (ATG101)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with Autophagy-related protein 101 (ATG101). CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Beclin 1-associated autophagy-related key regulator (ATG14)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and Beclin 1-associated autophagy-related key regulator (ATG14). CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Desmocollin-1 (DSC1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through Desmocollin-1 (DSC1) and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
Frizzled-10 (FZD10)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug PARPi Investigative
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Down regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model UWB1.289 Ovarian carcinoma Homo sapiens CVCL_B079
PEO1 Ovarian cystadenocarcinoma Homo sapiens CVCL_2686
In-vivo Model 2 × 107 PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Downregulation of m6A demethylases FTO and ALKBH5 was sufficient to increase Frizzled-10 (FZD10) mRNA m6A modification and reduce PARPi sensitivity, the finding elucidates a novel regulatory mechanism of PARPi resistance in EOC by showing that m6A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregulation of Wnt/Bete-catenin pathway.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug PARPi Investigative
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Down regulation
Pathway Response Wnt signaling pathway hsa04310
In-vitro Model UWB1.289 Ovarian carcinoma Homo sapiens CVCL_B079
PEO1 Ovarian cystadenocarcinoma Homo sapiens CVCL_2686
In-vivo Model 2 × 107 PARP inhibitor resistant PEO1 cells were suspended in 200 uL PBS : Matrigel (1:1) unilaterally injected subcutaneously into the right dorsal flank of 6-8 week-old female immunocompromised non-obese diabetic/severe combined immunodeficiency (NOD/SCID) gamma (NSG) mice. When the average tumor size reached ~100 mm3, the mice were then randomized into four groups and treated with vehicle control, Olaparib (50 mg/kg), XAV939 (5 mg/kg) or a combination daily for 18 days.
Thrombospondin-1 (THBS1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary IGFBP3 was shown to function as a suppressor of invasion in epithelial ovarian cancer (EOC). IGFBP3 could activate Thrombospondin-1 (THBS1) through promoter regulation mainly via an intracellular signaling pathway, such angiogenesis-regulating ability represents a major function of IGFBP3 as an onco-suppressor in the pathogenesis of ovarian cancer.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Insulin-like growth factor-binding protein 3 (IGFBP3) READER
Cell Process Cell proliferation
In-vitro Model OVTW59 (Ovarian cancer cell line)
OVTW59-P0 (Ovarian cancer cell line sub-lines)
OVTW59-P4 (Ovarian cancer cell line sub-lines)
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Severe combined immunodeficiency (SCID) female mice aged 6-8 weeks were transplanted subcutaneously with 2 × 107 P4-pBIG2i-hIGFBP3 or P4-pBIG2i transfectant cells. Tumor growth was measured using Vernier calipers and the volume was calculated using the formula: length × width × width × 0.52, which approximates the volume of an elliptical solid mass. Doxycycline at 2 mg/mL in drinking water with 2% sucrose was used to feed the animals when the tumor size was over 0.5 cm in diameter. The xenograft tumors were removed from five animals from each group on days 4, 7, 11, 14, and 20 after doxycycline treatment.
Tyrosine-protein kinase JAK2 (JAK2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating Tyrosine-protein kinase JAK2 (JAK2) m6A demethylation, promoting epithelial ovarian cancer resistance to cisplatin.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Responsed Drug Cisplatin Approved
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model HO8910-DDP (HO8910 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell lines HO8910-DDP)
HO-8910 Endocervical adenocarcinoma Homo sapiens CVCL_6868
A2780-DDP (A2780 underwent continuous stepwise exposure to increasing concentrations of cisplatin to create the cisplatin-resistant cell line)
A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
In-vivo Model About 5× 106 cells were injected subcutaneously into the axilla of the female athymic BALB/C nude mice (4 week-old, 18-20?g). When the average tumor size reached approximately 100mm3 (after 1 week), mice were then randomized into two groups and treated with cisplatin (5 mg/kg) or normal saline (NS) weekly.
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
RHPN1 antisense RNA 1 (head to head) (RHPN1-AS1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary RHPN1 antisense RNA 1 (head to head) (RHPN1-AS1)-miR-596-LETM1 axis plays a crucial role in epithelial ovarian cancer progression.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Cell proliferation and metastasis
In-vitro Model A2780 Ovarian endometrioid adenocarcinoma Homo sapiens CVCL_0134
Caov-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0201
ES2 Ewing sarcoma Homo sapiens CVCL_AX39
OV-90 Ovarian adenocarcinoma Homo sapiens CVCL_3768
OVCAR-3 Ovarian serous adenocarcinoma Homo sapiens CVCL_0465
In-vivo Model 1×106 ES-2-Scrambled or ES-2-shRHPN1-AS1 cells were injected subcutaneously on the right side of the mice.
hsa-miR-129-5p
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and hsa-miR-129-5p. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
hsa_circ_0005630 (circRAB11FIP1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary hsa_circ_0005630 (circRAB11FIP1) promoted autophagy flux of ovarian cancer through DSC1 and miR-129. CircRAB11FIP1 can serve as the possible marker for EOC diagnosis and treatment. CircRAB11FIP1 regulated the mechanism of autophagy through m6A modification and direct binding to mRNA. CircRAB11FIP1 bound to the mRNA of FTO and promoted its expression. CircRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. CircRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A.
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Autophagy hsa04140
Cell Process Cell autophagy
In-vitro Model SK-OV-3 Ovarian serous cystadenocarcinoma Homo sapiens CVCL_0532
In-vivo Model The SKOV3 ovarian cancer cell line was transfected with LV2-1 or LV2-NC. Thereafter, BALB/c nude mice (6-week old) were intraperitoneally injected with SKOV3 cells. The mice were killed after 5 weeks, and the number of ascites was determined.
References
Ref 1 CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129. Cell Death Dis. 2021 Feb 26;12(2):219. doi: 10.1038/s41419-021-03486-1.
Ref 2 N(6)-Methylation of Adenosine of FZD10 mRNA Contributes to PARP Inhibitor Resistance. Cancer Res. 2019 Jun 1;79(11):2812-2820. doi: 10.1158/0008-5472.CAN-18-3592. Epub 2019 Apr 9.
Ref 3 IGFBP3 inhibits angiogenesis through intracellular regulation of THBS1 expression. Am J Cancer Res. 2020 Jun 1;10(6):1728-1744. eCollection 2020.
Ref 4 ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer. J Exp Clin Cancer Res. 2021 Sep 8;40(1):284. doi: 10.1186/s13046-021-02088-1.
Ref 5 Long non-coding RNA RHPN1-AS1 promotes tumorigenesis and metastasis of ovarian cancer by acting as a ceRNA against miR-596 and upregulating LETM1. Aging (Albany NY). 2020 Mar 12;12(5):4558-4572. doi: 10.18632/aging.102911. Epub 2020 Mar 12.