The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression

Lv, Lei; Deng, Hui; Li, Y; Zhang, C; Liu, X; Liu, Q; Zhang, D; Wang, L; Pu, Youguang; Zhang, H; He, Yinghua; Wang, Y; Yu, Yipeng; Yu, Tsan-Jung; Zhu, Jiang

doi:10.1038/cddis.2014.367

Cited by 96 publications

(121 citation statements)

References 52 publications

(65 reference statements)

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“…It has been demonstrated that miRNAs are involved in regulating over 30 % of all human genes [5]. Thus, a single miRNA can control more than 100 genes' expression, which handles many cellular processes including cell proliferation, apoptosis, metastasis, and chemoresistance [6][7][8]. The dysregulated miRNA expression has been found in various cancers [9,10], which indicates that miRNAs are implicated in the tumor development and progression.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

et al. 2015

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Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

et al. 2015

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“…MiRNAs regulate the expression of a variety of target genes and their dysregulation is closely related to the development of diseases including cancer. The abnormal expression of miRNAs in cancer contributes to almost every field of tumor pathology [2, 3], including drug resistance [4], which remains a major obstacle to effective therapy of patients [5]. The multi-chemoresistance property differs dramatically among the cancer patients, even in the different cancer lesions of a single patient [6].…”

Section: Introductionmentioning

confidence: 99%

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

Zhao

Hou

et al. 2017

BMC Cancer

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BackgroundChemoresistance hinders the curative cancer chemotherapy. MicroRNAs (miRNAs) are key players in diverse biological processes including the chemoresistance of cancers.MethodsA RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells was performed to detect the levels of miR-34a-5p. Bioinformatics analysis revealed that AGTR1 is one of the target genes of miR-34a-5p. The mRNA and protein levels of AGTR1 were detected in both the miR-34a-5p-mimic transfected G-292 and miR-34a-5p-antagomiR transfected SJSA-1 cells. The involvement of AGTR1 with OS chemoresistance was validated by the experiments with siRNA-mediated repression or overexpression of the AGTR1 gene.ResultsWe showed that miR-34a-5p promotes the multi- chemoresistance of OS. The angiotensin II type 1 receptor (AGTR1) gene, is one of the targets of miR-34a-5p in OS and thus negatively correlates with OS chemoresistance by systematic investigations of a multi-drug sensitive (G-292) and resistant (SJSA-1) OS cell lines. Down-regulation of the AGTR1 expression by siRNA passivates G-292 cells and suppresses cell apoptosis, while over-expression of AGTR1 sensitizes SJSA-1 cells and thus promotes the drug-triggered cell death.ConclusionsThe miR-34a-5p and its target gene AGTR1 are the potential targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3002-x) contains supplementary material, which is available to authorized users.

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“…Furthermore, changes in alternative splicing of apoptotic genes influence sensitivity of cancer cells to chemotherapeutics, e.g., cisplatin or paclitaxel [44,45]. Interestingly, it was shown that SRSF2 contributes to chemoresistance in cancers of liver, bladder, and lung [46,47]. These observations suggest that SRSF2-mediated changes in apoptotic pathways may possibly contribute to resistance of renal cancer to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in Renal Cancer

Kędzierska

Popławski

Hoser

et al. 2016

IJMS

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Serine and arginine rich splicing factor 2(SRSF2) belongs to the serine/arginine (SR)-rich family of proteins that regulate alternative splicing. Previous studies suggested that SRSF2 can contribute to carcinogenic processes. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, highly aggressive and difficult to treat, mainly due to resistance to apoptosis. In this study we hypothesized that SRSF2 contributes to the regulation of apoptosis in ccRCC. Using tissue samples obtained from ccRCC patients, as well as independent validation on The Cancer Genome Atlas (TCGA) data, we demonstrate for the first time that expression of SRSF2 is decreased in ccRCC tumours when compared to non-tumorous control tissues. Furthermore, by employing a panel of ccRCC-derived cell lines with silenced SRSF2 expression and qPCR arrays we show that SRSF2 contributes not only to splicing patterns but also to expression of multiple apoptotic genes, including new SRSF2 targets: DIABLO, BIRC5/survivin, TRAIL, BIM, MCL1, TNFRSF9, TNFRSF1B, CRADD, BCL2L2, BCL2A1, and TP53. We also identified a new splice variant of CFLAR, an inhibitor of caspase activity. These changes culminate in diminished caspase-9 activity and inhibition of apoptosis. In summary, we show for the first time that decreased expression of SRSF2 in ccRCC contributes to protection of cancer cells viability.

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The DNA methylation-regulated miR-193a-3p dictates the multi-chemoresistance of bladder cancer via repression of SRSF2/PLAU/HIC2 expression

Cited by 96 publications

References 52 publications

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

MicroRNA-26b inhibits metastasis of osteosarcoma via targeting CTGF and Smad1

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in Renal Cancer

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