MiR‐34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin‐based chemotherapy

Xiao, Songshu; Li, Yueran; Pan, Qiong; Ye, Mingzhu; He, Songlin; Tian, Qiang; Xue, Min

doi:10.1002/jcb.26865

Cited by 39 publications

(28 citation statements)

References 37 publications

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“…14 MiR-34c targeted SOX9 and regulated the sensitivity of ovarian cancer cells to cisplatin-based chemotherapy. 15 Interestingly, the potential oncogenic function of miR-200a-3p in cancers was recently reported, which indicated the prognosis and therapeutic importance of miR-200a-3p in cancer. [16][17][18] However, the role of miR-200a-3p in ovarian cancer remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Shi¹,

Yang²,

Zhang³

et al. 2019

OTT

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Background: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized. Materials and methods: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3ʹ-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis. Results: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3ʹ-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells. Conclusion: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

Shi¹,

Yang²,

Zhang³

et al. 2019

OTT

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“…4f). Concordantly, miR-34c overexpression sensitized NPC cells to cisplatin-a phenotype corroborated in other cancer types [76][77][78][79].…”

Section: Discussionmentioning

confidence: 52%

MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma

et al. 2020

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Background: A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance. Methods: Two hundred forty-six NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666-1, were used for miR-34c gain-of-function and loss-of-function experiments. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay. Results: MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMTrepresentative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro. The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients. Conclusion: miR-34c is downregulated in NPC. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.

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“…Concordantly, miR-34c overexpression sensitized NPC cells to cisplatin-a phenotype corroborated in other cancer types [76][77][78][79].…”

Section: Discussionmentioning

confidence: 52%

MiR-34c Downregulation Leads to SOX4 Overexpression and Cisplatin Resistance in Nasopharyngeal Carcinoma

Bissey

Teng

Law

et al. 2020

Preprint

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Background : A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance. Methods: 246 NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666-1, were used to generate pre-miR-34c (gain-of-function) and anti-miR-34c (loss-of-function) cells. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay. Results: MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro . The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients. Conclusion: miR-34c downregulation correlates with higher incidence of DM. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.

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MiR‐34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin‐based chemotherapy

Cited by 39 publications

References 37 publications

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

<p>MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9</p>

MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma

MiR-34c Downregulation Leads to SOX4 Overexpression and Cisplatin Resistance in Nasopharyngeal Carcinoma

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