MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repression

Zhang, Jing; Liu, Lei; Sun, Yunyan; Xiang, Jiandong; Zhou, Dongmei; Wang, Li; Xu, Huali; Yang, Xiaoming; Du, Na; Zhang, Meng; Yan, Qin; Xi, Xiaowei

doi:10.18632/oncotarget.8530

Cited by 27 publications

(23 citation statements)

References 47 publications

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“…The Quantitative SYBR Green PCR Kit (Qiagen, Hilden, Germany) was used to quantify the Smad4 mRNA, E-cadherin and N-cadherin expression level respectively, GAPDH was used as the internal control. All the experiments were repeated at least triplicates [34, 37]. …”

Section: Materials and Methods Figure And Tablesmentioning

confidence: 99%

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

et al. 2016

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BackgroundTumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known.ResultsmiR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients.MethodsFive miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data.ConclusionsmiR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.

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Section: Materials and Methods Figure And Tablesmentioning

confidence: 99%

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

et al. 2016

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“…Moreover, DAPK2 is regulated at the transcriptional level by recruitment of several transcription factors to its promoter, such as Sp1, E2F1, KLF6 [39] and the myeloid master regulators PU.1 and C/EBPα [40]. Post-transcriptional regulation of DAPK2 expression by non-coding RNAs (ncRNAs) has been reported in the recent literature [41][42][43]. Here, we demonstrate that DAPK2 expression in colorectal cancer is controlled by miR-1285, thus providing further insight into the post-transcriptional layer of DAPK2 regulation.…”

Section: Discussionmentioning

confidence: 99%

miR-1285-3p Controls Colorectal Cancer Proliferation and Escape from Apoptosis through DAPK2

Villanova

Barbini

Piccolo

et al. 2020

IJMS

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MicroRNAs are tiny but powerful regulators of gene expression at the post-transcriptional level. Aberrant expression of oncogenic and tumor-suppressor microRNAs has been recognized as a common feature of human cancers. Colorectal cancer represents a major clinical challenge in the developed world and the design of innovative therapeutic approaches relies on the identification of novel biological targets. Here, we perform a functional screening in colorectal cancer cells using a library of locked nucleic acid (LNA)-modified anti-miRs in order to unveil putative oncogenic microRNAs whose inhibition yields a cytotoxic effect. We identify miR-1285-3p and further explore the effect of its targeting in both commercial cell lines and primary colorectal cancer stem cells, finding induction of cell cycle arrest and apoptosis. We show that DAPK2, a known tumor-suppressor, is a novel miR-1285 target and mediates both the anti-proliferative and the pro-apoptotic effects of miR-1285 depletion. Altogether, our findings uncover a novel oncogenic microRNA in colorectal cancer and lay the foundation for further studies aiming at the development of possible therapeutic strategies based on miR-1285 targeting.

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“…The staining intensity for AGGF1 was scored as follows: 0 (negative), 1 (weak), 2 (moderate), 3 (strong); and staining extent, based on the percentage of positively stained cells, was scored as follows: 0 (0%), 1 (1%-25%), 2 (26%-50%), 3 (51%-75%), 4 (76%-100%). The sum of intensity and extent score were used as the final staining score: 0-2, negative expression; 3-4, weak expression; and 5-7, strong expression [16,17]. The corresponding primary antibodies were: AGGF1 (1:100, Abcam, Cambridge, UK).…”

Section: Tissue Microarray (Tma) Construction and Immunohistochemicalmentioning

confidence: 99%

Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

Zhang

Sun

Chen

et al. 2019

Preprint

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Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the differential expression as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 236 CRC specimens and paired normal mucosae. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo. Conclusions: Our study demonstrates the aberrant overexpression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a potential therapeutic target for CRC patients, especially for CRC patients with distant metastasis.

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MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repression

Cited by 27 publications

References 47 publications

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4

miR-1285-3p Controls Colorectal Cancer Proliferation and Escape from Apoptosis through DAPK2

Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

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