Antisense Oligonucleotides against miR-21 Inhibit the Growth and Metastasis of Colorectal Carcinoma via the DUSP8 Pathway

Ding, Tao; Cui, Panpan; Zhou, Yue; Chen, Chao; Zhao, Juanjuan; Wang, Hairong; Guo, Ming; He, Zhixu; Xu, Lin

doi:10.1016/j.omtn.2018.09.004

Cited by 31 publications

(24 citation statements)

References 53 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that miRNAs are involved in tumorigenesis by modulating the expression of their target genes (7). Preceding studies revealed that miR-21 functions as a tumor suppressor or an oncogene in gastric carcinoma (21), colorectal carcinoma (22), hepatocellular carcinoma (23) and acute myeloid leukemias (13). In the present study, it was demonstrated that miR-21 was significantly upregulated and KLF5 was significantly downregulated in AML cells, compared with normal bone marrow cells.…”

Section: Discussionsupporting

confidence: 50%

MicroRNA‑21 promotes proliferation in acute myeloid leukemia by targeting Kr�ppel‑like factor�5

Hua

Yin

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

Abnormal expression of microRNA (miR)-21 has been reported in various types of cancers. However, the role and mechanism of miR-21 remain to be elucidated in acute myeloid leukemia (AML). In the present study, it was observed that miR-21 was upregulated and Krüppel-like factor 5 (KLF5) was downregulated in AML cells compared with normal bone marrow cells. Dual luciferase reporter assays revealed that KLF5 was a direct target of miR-21. Indeed, miR-21 overexpression resulted in a downregulation of KLF5 expression, while miR-21 inhibition had the opposite effect in AML cells. In addition, miR-21 overexpression promoted the proliferation of AML cells in vitro. Notably, using a mouse xenograft model, miR-21 overexpression was demonstrated to result in enhanced tumor growth and suppressed KLF5 expression in the xenograft tumors in vivo. In conclusion, the present results indicated that miR-21 promoted proliferation through directly regulating KLF5 expression in AML cells. miR-21 may thus serve as an oncogene in AML, providing a potential target for AML therapy.

show abstract

Section: Discussionsupporting

confidence: 50%

MicroRNA‑21 promotes proliferation in acute myeloid leukemia by targeting Kr�ppel‑like factor�5

Hua

Yin

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…ILK negatively regulates the expression of DUSP8 [39], a MAPK phosphatase upregulated in our study, and DUSP8 dephosphorylates and inactivates JNK [40,41]. Inhibition of ILK/AKT decreases miR-21 in vestibular schwannoma and meningioma cells [42], and targeting miR-21 with antisense oligonucleotides (ASOs) inhibits growth and metastasis via upregulation of DUSP8 in colorectal carcinoma [43]. MARVELD3, a transmembrane protein of tight junctions [44,45] upregulated in our study, inhibits JNK activity via recruitment of MEKK1 to cell junctions [46].…”

Section: Discussionmentioning

confidence: 90%

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Reyes-González

Quiñones-Díaz

Santana

et al. 2020

Cancers

View full text Add to dashboard Cite

Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop platinum-resistant disease with poor prognosis. Although reports suggest that integrin-linked kinase (ILK) is a potential target for ovarian cancer treatment, identification of ILK downstream effectors has not been fully explored. The purpose of this study was to investigate the molecular and biological effects of targeting ILK in cisplatin-resistant ovarian cancer. Western blot analysis showed that phosphorylation levels of ILK were higher in cisplatin-resistant compared with cisplatin-sensitive ovarian cancer cells. Further immunohistochemical analysis of ovarian cancer patient samples showed a significant increase in phosphorylated ILK levels in the tumor tissue when compared to normal ovarian epithelium. Targeting ILK by small-interfering RNA (siRNA) treatment reduced cisplatin-resistant cell growth and invasion ability, and increased apoptosis. Differential gene expression analysis by RNA sequencing (RNA-Seq) upon ILK-siRNA transfection followed by Ingenuity Pathway Analysis (IPA) and survival analysis using the Kaplan–Meier plotter database identified multiple target genes involved in cell growth, apoptosis, invasion, and metastasis, including several non-coding RNAs. Taken together, results from this study support ILK as an attractive target for ovarian cancer and provide potential ILK downstream effectors with prognostic and therapeutic value.

show abstract

“…For instance, Wei et al reported that MALAT1-shRNA treatment alleviated the in ammatory injury after lung transplant ischemia-reperfusion by downregulating IL-8 and inhibiting in ltration and activation of neutrophils [47]. Similarly, our previous work also showed that ASOs against miR-21 could reduce the growth and metastasis of human CRC cells in vivo and in vitro [48]. To evaluate the potential value of MAPK4 targeting in ALI treatment, herein, we assessed the possible effects of MAPK4-shRNA pre-treatment on the pathology of ALI.…”

Section: Discussionmentioning

confidence: 70%

Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

Mao

Zhou

Chen

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Acute lung injury (ALI) is a serious disease with highly morbidity and mortality that causes serious health problems worldwide. Atypical mitogen activated protein kinases (MAPKs) play critical roles in the development of tissues and have been proposed as promising therapeutic targets for various diseases. However, the potential role of atypical MAPKs in ALI remains elusive. In this study, we investigated the role of atypical MAPKs family member MAPK4 in ALI using LPS-induced murine ALI model. Results: We found that MAPK4 deficiency mice exhibited prolonged survival time after LPS challenge, accompanied by alleviated pathology in lung tissues, decreased levels of pro-inflammatory cytokines and altered composition of immune cells in BALF. Furthermore, the transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK pathways, was reduced obviously in LPS-treated MAPK4-/- mice. Notably, the expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not related with MAPK4 promoter methylation, but negatively orchestrated by transcriptional factors NFKB1 and NR3C1. Further studies have shown that the expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in macrophage in response to LPS treatment. Finally, MAPK4 inhibition using shRNA pre-treatment could ameliorate the pathology of lung tissues and prolong the survival time of mice after LPS challenge. Conclusions: Collectively, these findings reveal an important biological function of atypical MAPK in mediating the pathology of ALI, indicating that MAPK4 might be a novel potential therapeutic target for ALI treatment.

show abstract

Antisense Oligonucleotides against miR-21 Inhibit the Growth and Metastasis of Colorectal Carcinoma via the DUSP8 Pathway

Cited by 31 publications

References 53 publications

MicroRNA‑21 promotes proliferation in acute myeloid leukemia by targeting Kr�ppel‑like factor�5

MicroRNA‑21 promotes proliferation in acute myeloid leukemia by targeting Kr�ppel‑like factor�5

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Identification of Atypical Mitogen-Activated Protein Kinase MAPK4 as A Novel Regulator in Acute Lung Injury

Contact Info

Product

Resources

About