MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1

Liu, Hui; Cheng, Xiaojuan

doi:10.18632/oncotarget.24380

Cited by 30 publications

(19 citation statements)

References 45 publications

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“…Through the growth inhibition assay, we found that the IC50 value of the control group was 3.068 times higher than that of the SPIB overexpression group, indicating that the high expression of SPIB could increase the sensitivity of CRC cells to oxaliplatin. Since the activation of JNK can promote oxaliplatin induced apoptosis [16], we believe that the high expression of SPIB induces the sensitivity of CRC cells to oxaliplatin by activating the JNK pathway. 5-FU is a commonly used chemotherapy drug in tumor therapy [17], which mainly targets at the S phase of cell cycle and other phases to play an anti-tumor role [18].…”

Section: Discussionmentioning

confidence: 98%

SPIB Acts as a Tumor Suppressor by Activating NFkB and JNK Signaling Pathways Through MAP4K1 in Colorectal Cancer Cells

Zhao

Yuan

et al. 2020

Preprint

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BackgroundColorectal cancer (CRC) is one of the major cancers in the world. Spi-B Transcription Factor (SPIB) is one member of the E-twenty-six (ETS) transcription factor family. Previous studies have shown that the expression of SPIB is down-regulated in human colorectal cancer tissues. However, its biological function in colorectal cancer cells is not reported. The purpose of our study is to explore the biological function and related mechanism of SPIB in colorectal cancer cells, to provide reference for the molecular detection and targeted drug therapy of colorectal cancer.MethodsThe biological function of SPIB in colorectal cancer cells were studied by colony formation assay, CCK-8 cell proliferation assay, transwell assay, tube formation assay, flow cytometry analysis. Growth inhibition assay was used to measure the impact of SPIB on oxaliplatin and 5-fluorouracil (5-FU). Double luciferase reporter assay and western blot were used to detect mechanism of SPIB in colorectal cancer cells. ResultsSPIB mRNA was down-regulated in CRC cell lines and CRC tissues. SPIB can inhibit the proliferation, migration and invasion of CRC cells; can inhibit angiogenesis; and induce the cell cycle of CRC cells arrest in G2/M phase and promote the apoptosis of CRC cells. In the growth inhibition assay we found that compared with the control group, the 50% inhibitory concentration(IC50) values of oxaliplatin and 5-FU in the SPIB overexpression group were significantly reduced. Western blot results showed that the overexpression of SPIB up-regulated cleaved-PARP(c-PARP), nuclear factor kB p65 (NFkB p65), phospho-NFkB p65(p-NFkB P65), JNK1, and C-Jun proteins expression level compared with the control group. Double luciferase report experiment showed that SPIB can activate the promoter of MAP4K1 and enhance the expression of MAP4K1. After silencing MAP4K1, the protein expressions of c-PARP, NFkB P65, p-NFkB P65, JNK1, and C-Jun were down-regulated. ConclusionsIn this study, we found that SPIB is a tumor suppressor in colorectal cancer cells, SPIB sensitizes colorectal cancer cells to oxaliplatin and 5-FU. we also found that MAP4K1 is a target gene of SPIB, SPIB exerts its anti-colorectal cancer effect by activating NFkB and JNK signaling pathways through MAP4K1. The above findings may provide reference for new molecular markers and therapeutic targets for CRC.

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Section: Discussionmentioning

confidence: 98%

SPIB Acts as a Tumor Suppressor by Activating NFkB and JNK Signaling Pathways Through MAP4K1 in Colorectal Cancer Cells

Zhao

Yuan

et al. 2020

Preprint

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“…Therefore, miR-29b is considered as a tumor marker for the prognosis of CRC. In previous studies on tumor chemotherapy drug resistance, miR-29b was found to reverse Oxa resistance of CRC cells by targeting the SIRT1/ROS/JNK pathway [ 46 ], moreover, it can also target FOLR1 to inhibit cell growth of colon cancer cells and increases cell sensitivity to Oxa [ 47 ]. Our experimental results further complement these previous findings.…”

Section: Discussionmentioning

confidence: 99%

Overexpressed GATA3 enhances the sensitivity of colorectal cancer cells to oxaliplatin through regulating MiR-29b

Wang

et al. 2020

Cancer Cell Int

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Background GATA binding protein 3 (GATA3) and miR-29b are related to colorectal cancer (CRC). The current study explored the regulatory relationship between GATA3 and miR-29b, and the mechanism of the two in the drug resistance of CRC cells to oxaliplatin. Method Apoptosis of CRC cells induced by oxaliplatin at various doses was detected by flow cytometry. CRC cells were separately transfected with overexpression and knockdown of GATA3, miR-29b agomir and antagomir, and treated by oxaliplatin to detect the cell viability and apoptosis by performing Cell Couting Kit-8 (CCK-8) and flow cytometry. The expression levels of GATA3, caspase3 and cleaved caspase3 were determined by Western blot, and the expression of miR-29b was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Animal experiments were performed to examine the changes of transplanted tumors in nude mouse xenograft studies and observed by in vivo imaging. TUNEL staining was performed to detect tumor cell apoptosis. Result Both GATA3 and miR-29b agomir inhibited the activity of the CRC cells, promoted apoptosis and Cleaved caspase3 expression, and reduced the resistance of the cells to chemotherapy drug oxaliplatin. Although GATA3 could up-regulate miR-29b expression, the tumor-suppressive effect of GATA3 was partially reversed by miR-29b antagomir. In vivo experiments showed that down-regulating the expression of GATA3 promoted the growth rate and volume of transplanted tumors, while overexpressing GATA3 had no significant effect on tumor growth. TUNEL staining results showed that knocking down or overexpression of GATA3 did not cause significant changes to apoptotic bodies of CRC cells, while oxaliplatin treatment increased the number of apoptotic bodies. Conclusion GATA3 inhibits the cell viability of CRC cells, promotes apoptosis, and reduces oxaliplatin resistance of CRC cells through regulating miR-29b.

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“…miR-29b has been documented to negatively affect tumorigenesis and cancer progression by regulating cell proliferation, survival, and metastasis 28 , Whilst overexpression of miR-29b can also inhibit tumorigenesis 35 and angiogenesis 36 - 38 . Moreover, miR-29b can reverse drug resistance in ovarian cancer 39 , 40 and colorectal cancer 41 , as well as radioresistance in cervical cancer 42 . In this study, we found that overexpression of miR-29b-3p reduced cell viability, suppressed cell proliferation, and decreased colony formation, resulting in increased sensitivity of LNCaP cells to X-rays irradiation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells

Mao¹,

Tang²,

Tang³

et al. 2020

J. Cancer

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Radiotherapy is frequently applied for clinically localized prostate cancer while its efficacy could be significantly hindered by radioresistance. MicroRNAs (miRNAs) are important regulators in mediating cellular responses to ionizing radiation (IR), and strongly associate with radiosensitivity in many cancers. In this study, enhancement of radiosensitivity by miR-29b-3p was demonstrated in prostate cancer cell line LNCaP in vitro. Results showed that miR-29b-3p expression was significantly upregulated in response to IR from both X-rays and carbon ion irradiations. Knockdown of miR-29b-3p resulted in radioresistance while overexpression of miR-29b-3p led to increased radiosensitivity (showing reduced cell viability, suppressed cell proliferation and decreased colony formation). In addition, miR-29b-3p was found to directly target Wnt1-inducible-signaling protein 1 (WISP1). Inhibition of WISP1 facilitated the mitochondrial apoptosis pathway through suppressing Bcl-XL expression while activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The results indicated that miR-29b-3p was a radiosensitizing miRNAs and could enhance radiosensitivity of LNCaP cells by targeting WISP1. These findings suggested a novel treatment to overcome radioresistance in prostate cancer patients, especially those with higher levels of the WISP1 expression.

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MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1

Cited by 30 publications

References 45 publications

SPIB Acts as a Tumor Suppressor by Activating NFkB and JNK Signaling Pathways Through MAP4K1 in Colorectal Cancer Cells

SPIB Acts as a Tumor Suppressor by Activating NFkB and JNK Signaling Pathways Through MAP4K1 in Colorectal Cancer Cells

Overexpressed GATA3 enhances the sensitivity of colorectal cancer cells to oxaliplatin through regulating MiR-29b

MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells

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