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Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2019

04.09.2019 | Original Article – Cancer Research

METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy

verfasst von: Lin Xin, Qi Zhou, Yi-Wu Yuan, Li-Qiang Zhou, Li Liu, Shi-Hao Li, Chuan liu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2019

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Abstract

Background

Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear.

Materials and methods

Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay.

Results

Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo.

Conclusion

METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
Literatur
Zurück zum Zitat An Y, Zhang Z, Shang Y, Jiang X, Dong J, Yu P, Nie Y, Zhao Q (2015) miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell Death Dis 6:e1766CrossRefPubMedPubMedCentral An Y, Zhang Z, Shang Y, Jiang X, Dong J, Yu P, Nie Y, Zhao Q (2015) miR-23b-3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell Death Dis 6:e1766CrossRefPubMedPubMedCentral
Zurück zum Zitat Chen S, Wu D-D, Sang X-B, Wang L-L, Zong Z-H, Sun K-X, Liu B-L, Zhao Y (2017) The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma. Cell Death Dis 8:e3118CrossRefPubMedPubMedCentral Chen S, Wu D-D, Sang X-B, Wang L-L, Zong Z-H, Sun K-X, Liu B-L, Zhao Y (2017) The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma. Cell Death Dis 8:e3118CrossRefPubMedPubMedCentral
Zurück zum Zitat Hu J, Cheung N-KV (2009) Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drugs. Int J Cancer 124:1700–1706CrossRefPubMedPubMedCentral Hu J, Cheung N-KV (2009) Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drugs. Int J Cancer 124:1700–1706CrossRefPubMedPubMedCentral
Zurück zum Zitat Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Murakami T, Kiyuna T, Miyake K, Miyake M, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Singh SR, Eilber FC, Hoffman RM (2018) Recombinant methioninase in combination with doxorubicin (DOX) overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma. Cancer Lett 417:168–173CrossRefPubMed Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Murakami T, Kiyuna T, Miyake K, Miyake M, Singh AS, Eckardt MA, Nelson SD, Russell TA, Dry SM, Li Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Tsuchiya H, Singh SR, Eilber FC, Hoffman RM (2018) Recombinant methioninase in combination with doxorubicin (DOX) overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma. Cancer Lett 417:168–173CrossRefPubMed
Zurück zum Zitat Kawaguchi K, Igarashi K, Li S, Han Q, Tan Y, Miyake K, Kiyuna T, Miyake M, Murakami T, Chmielowski B, Nelson SD, Russell TA, Dry SM, Li Y, Unno M, Eilber FC, Hoffman RM (2017) Recombinant methioninase (rMETase) is an effective therapeutic for BRAF-V600E-negative as well as -positive melanoma in patient-derived orthotopic xenograft (PDOX) mouse models. Oncotarget 9:915–923PubMedPubMedCentral Kawaguchi K, Igarashi K, Li S, Han Q, Tan Y, Miyake K, Kiyuna T, Miyake M, Murakami T, Chmielowski B, Nelson SD, Russell TA, Dry SM, Li Y, Unno M, Eilber FC, Hoffman RM (2017) Recombinant methioninase (rMETase) is an effective therapeutic for BRAF-V600E-negative as well as -positive melanoma in patient-derived orthotopic xenograft (PDOX) mouse models. Oncotarget 9:915–923PubMedPubMedCentral
Zurück zum Zitat Kawaguchi K, Han Q, Li S, Tan Y, Igarashi K, Miyake K, Kiyuna T, Miyake M, Chemielwski B, Nelson SD, Russell TA, Dry SM, Li Y, Singh AS, Eckardt MA, Unno M, Eilber FC, Hoffman RM (2018a) Intra-tumor l-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models. Oncotarget 9:11119–11125PubMedPubMedCentral Kawaguchi K, Han Q, Li S, Tan Y, Igarashi K, Miyake K, Kiyuna T, Miyake M, Chemielwski B, Nelson SD, Russell TA, Dry SM, Li Y, Singh AS, Eckardt MA, Unno M, Eilber FC, Hoffman RM (2018a) Intra-tumor l-methionine level highly correlates with tumor size in both pancreatic cancer and melanoma patient-derived orthotopic xenograft (PDOX) nude-mouse models. Oncotarget 9:11119–11125PubMedPubMedCentral
Zurück zum Zitat Kawaguchi K, Miyake K, Han Q, Li S, Tan Y, Igarashi K, Lwin TM, Higuchi T, Kiyuna T, Miyake M, Oshiro H, Bouvet M, Unno M, Hoffman RM (2018b) Targeting altered cancer methionine metabolism with recombinant methioninase (rMETase) overcomes partial gemcitabine-resistance and regresses a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer. Cell Cycle 17:868–873CrossRefPubMedPubMedCentral Kawaguchi K, Miyake K, Han Q, Li S, Tan Y, Igarashi K, Lwin TM, Higuchi T, Kiyuna T, Miyake M, Oshiro H, Bouvet M, Unno M, Hoffman RM (2018b) Targeting altered cancer methionine metabolism with recombinant methioninase (rMETase) overcomes partial gemcitabine-resistance and regresses a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer. Cell Cycle 17:868–873CrossRefPubMedPubMedCentral
Zurück zum Zitat Kawaguchi K, Han Q, Li S, Tan Y, Igarashi K, Murakami T, Unno M, Hoffman RM (2019) Efficacy of recombinant methioninase (rMETase) on recalcitrant cancer patient-derived orthotopic xenograft (PDOX) mouse models: a review. Cells 8 Kawaguchi K, Han Q, Li S, Tan Y, Igarashi K, Murakami T, Unno M, Hoffman RM (2019) Efficacy of recombinant methioninase (rMETase) on recalcitrant cancer patient-derived orthotopic xenograft (PDOX) mouse models: a review. Cells 8
Zurück zum Zitat Kongsema M, Zona S, Karunarathna U, Cabrera E, Man EPS, Yao S, Shibakawa A, Khoo US, Medema RH, Freire R, Lam EWF (2016) RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment. Oncogenesis 5:e252CrossRefPubMedPubMedCentral Kongsema M, Zona S, Karunarathna U, Cabrera E, Man EPS, Yao S, Shibakawa A, Khoo US, Medema RH, Freire R, Lam EWF (2016) RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment. Oncogenesis 5:e252CrossRefPubMedPubMedCentral
Zurück zum Zitat Kumar A, Singh UK, Chaudhary A (2015) Targeting autophagy to overcome drug resistance in cancer therapy. Future medicinal chemistry 7:1535–1542CrossRefPubMed Kumar A, Singh UK, Chaudhary A (2015) Targeting autophagy to overcome drug resistance in cancer therapy. Future medicinal chemistry 7:1535–1542CrossRefPubMed
Zurück zum Zitat Li X, Liang J, Liu YX, Wang Y, Yang XH, Bao H, Zhang GL, Du J, Wu XH (2016) Knockdown of the FoxM1 enhances the sensitivity of gastric cancer cells to cisplatin by targeting Mcl-1. Pharmazie 71:345–348PubMed Li X, Liang J, Liu YX, Wang Y, Yang XH, Bao H, Zhang GL, Du J, Wu XH (2016) Knockdown of the FoxM1 enhances the sensitivity of gastric cancer cells to cisplatin by targeting Mcl-1. Pharmazie 71:345–348PubMed
Zurück zum Zitat Liu Y, Feng J, Sun M, Yang G, Yuan H, Wang Y, Bu Y, Zhao M, Zhang S, Zhang X (2019) Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma. Cancer Lett 454:158–170CrossRefPubMed Liu Y, Feng J, Sun M, Yang G, Yuan H, Wang Y, Bu Y, Zhao M, Zhang S, Zhang X (2019) Long non-coding RNA HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related hepatocellular carcinoma. Cancer Lett 454:158–170CrossRefPubMed
Zurück zum Zitat Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F (2014) Treatment of gastric cancer. World J Gastroenterol 20:1635–1649CrossRefPubMedPubMedCentral Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F (2014) Treatment of gastric cancer. World J Gastroenterol 20:1635–1649CrossRefPubMedPubMedCentral
Zurück zum Zitat Pasini F, Fraccon AP (2011) The role of chemotherapy in metastatic gastric cancer. Anticancer Res 31:3543–3554PubMed Pasini F, Fraccon AP (2011) The role of chemotherapy in metastatic gastric cancer. Anticancer Res 31:3543–3554PubMed
Zurück zum Zitat Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 8:7–30CrossRef Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 8:7–30CrossRef
Zurück zum Zitat Su W, Tang J, Wang Y, Sun S, Shen Y, Yang H (2019) Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma. J Cell Mol Med 23:2645–2655CrossRefPubMedPubMedCentral Su W, Tang J, Wang Y, Sun S, Shen Y, Yang H (2019) Long non-coding RNA highly up-regulated in liver cancer promotes epithelial-to-mesenchymal transition process in oral squamous cell carcinoma. J Cell Mol Med 23:2645–2655CrossRefPubMedPubMedCentral
Zurück zum Zitat Tian L, Zhao Z, Xie L, Zhu J (2017) MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. Oncotarget 9:4886–4896PubMedPubMedCentral Tian L, Zhao Z, Xie L, Zhu J (2017) MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. Oncotarget 9:4886–4896PubMedPubMedCentral
Zurück zum Zitat Wu H, Qiao F, Zhao Y, Wu S, Hu M, Wu T, Huang F, Chen W, Sun D, Liu M, Zhao J (2019) Downregulation of long non-coding RNA FALEC inhibits gastric cancer cell migration and invasion through impairing ECM1 expression by exerting its enhancer-like function. Front Genet 10:255CrossRefPubMedPubMedCentral Wu H, Qiao F, Zhao Y, Wu S, Hu M, Wu T, Huang F, Chen W, Sun D, Liu M, Zhao J (2019) Downregulation of long non-coding RNA FALEC inhibits gastric cancer cell migration and invasion through impairing ECM1 expression by exerting its enhancer-like function. Front Genet 10:255CrossRefPubMedPubMedCentral
Zurück zum Zitat Xi Z, Si J, Nan J (2019) LncRNA MALAT1 potentiates autophagyassociated cisplatin resistance by regulating the microRNA30b/autophagyrelated gene 5 axis in gastric cancer. Int J Oncol 54:239–248PubMed Xi Z, Si J, Nan J (2019) LncRNA MALAT1 potentiates autophagyassociated cisplatin resistance by regulating the microRNA30b/autophagyrelated gene 5 axis in gastric cancer. Int J Oncol 54:239–248PubMed
Zurück zum Zitat Xin L, Yang W-F, Zhang H-T, Li Y-F, Liu C (2018a) The mechanism study of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin. Br J Cancer 118:1189–1199CrossRefPubMedPubMedCentral Xin L, Yang W-F, Zhang H-T, Li Y-F, Liu C (2018a) The mechanism study of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin. Br J Cancer 118:1189–1199CrossRefPubMedPubMedCentral
Zurück zum Zitat Xin X, Wu M, Meng Q, Wang C, Lu Y, Yang Y, Li X, Zheng Q, Pu H, Gui X, Li T, Li J, Jia S, Lu D (2018b) Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer 17:94CrossRefPubMedPubMedCentral Xin X, Wu M, Meng Q, Wang C, Lu Y, Yang Y, Li X, Zheng Q, Pu H, Gui X, Li T, Li J, Jia S, Lu D (2018b) Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer 17:94CrossRefPubMedPubMedCentral
Zurück zum Zitat Xin L, Zhou L-Q, Liu L, Yuan Y-W, Zhang H-T, Zeng F (2019) METase promotes cell autophagy via promoting SNHG5 and suppressing miR-20a in gastric cancer. Int J Biol Macromol 122:1046–1052CrossRefPubMed Xin L, Zhou L-Q, Liu L, Yuan Y-W, Zhang H-T, Zeng F (2019) METase promotes cell autophagy via promoting SNHG5 and suppressing miR-20a in gastric cancer. Int J Biol Macromol 122:1046–1052CrossRefPubMed
Zurück zum Zitat Xiong H, Ni Z, He J, Jiang S, Li X, He J, Gong W, Zheng L, Chen S, Li B, Zhang N, Lyu X, Huang G, Chen B, Zhang Y, He F (2017) LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene 36:3528CrossRefPubMed Xiong H, Ni Z, He J, Jiang S, Li X, He J, Gong W, Zheng L, Chen S, Li B, Zhang N, Lyu X, Huang G, Chen B, Zhang Y, He F (2017) LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells. Oncogene 36:3528CrossRefPubMed
Zurück zum Zitat YiRen H, YingCong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, Ende C, XiZhou L, Yanfan C (2017) Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer. Mol Cancer 16:174CrossRefPubMedPubMedCentral YiRen H, YingCong Y, Sunwu Y, Keqin L, Xiaochun T, Senrui C, Ende C, XiZhou L, Yanfan C (2017) Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer. Mol Cancer 16:174CrossRefPubMedPubMedCentral
Zurück zum Zitat Yu G, Xiong D, Liu Z, Li Y, Chen K, Tang H (2019) Long noncoding RNA LINC00052 inhibits colorectal cancer metastasis by sponging microRNA-574-5p to modulate CALCOCO1 expression. J Cell Biochem 1:1 Yu G, Xiong D, Liu Z, Li Y, Chen K, Tang H (2019) Long noncoding RNA LINC00052 inhibits colorectal cancer metastasis by sponging microRNA-574-5p to modulate CALCOCO1 expression. J Cell Biochem 1:1
Zurück zum Zitat Zhang Y, Song X, Wang X, Hu J, Jiang L (2016) Silencing of LncRNA HULC enhances chemotherapy induced apoptosis in human gastric cancer. J Med Biochem 35:137–143CrossRefPubMedPubMedCentral Zhang Y, Song X, Wang X, Hu J, Jiang L (2016) Silencing of LncRNA HULC enhances chemotherapy induced apoptosis in human gastric cancer. J Med Biochem 35:137–143CrossRefPubMedPubMedCentral
Metadaten
Titel
METase/lncRNA HULC/FoxM1 reduced cisplatin resistance in gastric cancer by suppressing autophagy
verfasst von
Lin Xin
Qi Zhou
Yi-Wu Yuan
Li-Qiang Zhou
Li Liu
Shi-Hao Li
Chuan liu
Publikationsdatum
04.09.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-03015-w

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