Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma

Yang, Hongwei; Liu, Guanghui; Liu, Yuqiong; Zhao, Hongchao; Yang, Zhen; Zhao, Chunlin; Zhang, Xiefu; Ye, Hua

doi:10.1016/j.biopha.2016.06.057

Cited by 44 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, our results also demonstrated that the capacities of proliferation, invasion, migration, and antiapoptosis, in addition to Bcl‐2 expression were promoted in the miR‐940 mimic, siRNA‐ SFRP1 , and LiCl groups, while the expression of Fas and Bax was significantly reduced when compared with the NC and blank groups; these results could be reversed by miR‐940 inhibitor. miR‐940 has been reported to inhibit cellular proliferation and migration in triple‐negative breast cancer, to enhance progression of cervical cancer by repressing p27 and PTEN and to facilitate invasion and proliferation of pancreatic cancer cells by inhibiting GSK3β and SFRP1 . Shih et al confirmed that the SFRP1 expression functioning as an antagonist of the Wnt pathway provides a purported mechanism to suppress the abnormal activation of this pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Secreted frizzled‐related protein 1 ( SFRP1 ) belongs to the family of SFRPs, the secreted glycoproteins, and acts as a critical tumor suppressor through downregulating β‐catenin . There is a study supporting that miR‐940 knockdown could significantly elevate GSK3β and SFRP1 expression and in turn repress Wnt/β‐catenin‐mediated cell invasion, migration, metastasis, and proliferation in the development of pancreatic carcinoma . Evidence indicates that Wnt/β‐catenin signaling pathway involves in maintenance and development of many tissues and organs, including bone .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Lin

Zhang

Jiang

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Osteosarcoma (OS) is the most common malignant tumor of bone with a high potential for metastasis. This study intends to explore whether microRNA‐940 (miR‐940) affects the development of OS cells and the underlying mechanism. OS and adjacent normal tissues were collected from OS patients; the OS cell line with the highest expression of miR‐940 was selected, which was then subjected to transfection of miR‐940 mimic, miR‐940 inhibitor, siRNA‐secreted frizzled‐related protein 1 (SFRP1) or LiCl (agonists of Wnt/β‐catenin pathway) to identify regulation of miR‐940 to OS cells through SFRP1. The targeting relationship between miR‐940 and SFRP1 was verified using dual‐luciferase reporter gene assay. Reverse‐transcription quantitative polymerase chain reaction and Western blot assay were performed to determine miR‐940, SFRP1, β‐catenin, and cyclinD1 and apoptosis‐related genes Fas, Bax, and Bcl‐2. MTT (3‐(4, 5‐dimethylthiazol‐2‐Yl)‐2, 5‐diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively. Nude mice models were established to observe the tumor formation. Higher expression of miR‐940, β‐catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR‐940 targeted and negatively regulated SFRP1 expression. Furthermore, upregulated miR‐940 expression activated the Wnt/β‐catenin signaling pathway in OS. With the treatment of miR‐940 mimic, LiCL, or siRNA‐SFRP1, OS cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated Bcl‐2 expression and reduced Fas and Bax expression). The study demonstrates that miR‐940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human OS cells by downregulating SFRP1 through activating Wnt/β‐catenin signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Lin

Zhang

Jiang

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…The SFRPs encode a family of secreted proteins with a cysteine‐rich domain homologous to the Wnt‐binding domain of FZD receptor proteins, which act as well‐established inhibitory regulators of the Wnt signaling pathway (Zhao et al, ). SFRP1 is a member of this protein family and it is downregulated in a multitude of cancers (Afgar et al, ; Yang et al, ). More recent data have suggested that SFRP1 may play an important role in controlling inflammation (Barandon et al, ; Ehrlund et al, ).…”

Section: Discussionmentioning

confidence: 99%

Secreted frizzled‐related protein 1 regulates the progression of neuropathic pain in mice following spinal nerve ligation

Tang

Jin

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Previous studies have shown that the Wnt/β-catenin signaling pathway plays an important role in modulating neuropathic pain after sciatic nerve injury. In this study, we explored the role of secreted frizzled-related protein 1 (SFRP1), a Wnt antagonist, in neuropathic pain using a mouse model following spinal nerve ligation (SNL). We found SNL-induced SFRP1 downregulation in the spinal cord. Further, overexpression of SFRP1 via spinal injection into the spinal cord attenuated SNL-induced allodynia, hyperalgesia, and neuroinflammation. Consistently, in vitro assays also showed decreased expression of SFRP1 in spinal cord astrocytes after exposure to lipopolysaccharide (LPS). Overexpression of SFRP1 significantly alleviated the secretion of LPS-induced proinflammatory factors in spinal cord astrocytes. Furthermore, spinal injection of LPS-treated astrocytes induced allodynia and hyperalgesia, which were reversed by the overexpression of SFRP1 in these cells. Additionally, SNL increased Wnt3a and β-catenin levels and also induced an increase in nuclear expression of β-catenin; these effects were all attenuated by SFRP1. Finally, we found that downregulation of SFRP1, mainly through DNA methylation, is involved in the pathogenesis of neuropathic pain. Taken together, these results suggested that the SFRP1/Wnt3a/β-catenin signaling pathway might be a suitable therapeutic target for neuropathic pain.

show abstract

“…The knockdown of miR-940 restored MKP1 and MKK4 expression and attenuated cisplatin resistance in lung cancer. Paradoxically, miR-940 has been demonstrated to promote tumor cell invasion and metastasis by downregulating GSK3β/sFRP1 [60] and ZNF24 in gastric cancer [61], respectively. However, the clinical significance of miR-940 and the biological roles of miR-940 and its direct functional targets in OC has not yet been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Rashed

Kanlikilicer²,

Rodríguez-Aguayo³

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype.

show abstract

Over-expression of microRNA-940 promotes cell proliferation by targeting GSK3β and sFRP1 in human pancreatic carcinoma

Cited by 44 publications

References 30 publications

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway

Secreted frizzled‐related protein 1 regulates the progression of neuropathic pain in mice following spinal nerve ligation

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

Contact Info

Product

Resources

About