Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy

Zhai, Haiyan; Fesler, Andrew; Ba, Yue; Wu, Song; Ju, Jingfang

doi:10.18632/oncotarget.3771

Cited by 123 publications

(97 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By targeting various targets, miR-140-5p has shown to critically involve in tumor cell proliferation, apoptosis, vascularization, migration and invasion. These previously confirmed targets includes Sp1 [9], IGF1R [11], MMD [12], HDAC4 [13], Smad2 [14], TGFBR1 [15], FGF9 [15], SOX2 [16], Slug [17], BMP2 [19], Smad3 [20], and ADAMTS5 [21]. Although miR-140-5p is generally accepted as a tumor suppressor, an oncogenic role of miR-140-5p has also been implicated depending on different cell context.…”

Section: Introductionmentioning

confidence: 83%

“…It is encoded within intron 16 of Wwp2, an E3 ubiquitin ligase on chromosome 16 [9]. Expression profiling of tumors and normal tissues has revealed a possible tumor suppressive role for miR-140-5p in many cancers, including ovarian cancer [10], lung cacner [11,12], CRC [13,14], osteosarcoma [13], hepatocellular carcinoma [15], breast cancer [16], esophageal cancer [17] and basal cell carcinoma [18]. By targeting various targets, miR-140-5p has shown to critically involve in tumor cell proliferation, apoptosis, vascularization, migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

“…Zhai et al demonstrated that overexpression of miR-140-5p abolished tumor formation and metastasis in colon cancer stem cells by directly targeting Smad2 [14]. A progressive loss of miR-140-5p expression was also revealed from normal colorectal mucosa to primary tumor tissues, with further reduction in liver metastatic tissues.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

show abstract

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Zhai et al showed that the tumor formation and metastasis ability of colon cancer stem cells can be abolished by the overexpression of miR-140-5p, which directly affected a target known as Smad2 [15]. In addition, primary tumor tissues showed a progressive loss in miR-140-5p expression as compared with that in normal colorectal mucosa, whereas tissues affected by liver metastasis were associated with a further decreased expression of miR-140-5p.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, an elevated miR-140-5p expression was found to be closely related to a better prognosis in stage III and IV CRC patients. In contrast, Mosakhani et al discovered that the up-regulation of miR-140-5p was closely associated with worse overall survival in metastatic CRC patients harboring a wild type KRAS/BRAF [15]. In addition, downregulated miR-140-5p expression was closely related to poorer overall survival, an advanced clinical stage and lymph node metastasis [16].…”

Section: Discussionmentioning

confidence: 99%

A functional Variant (Rs35592567) in TP63 at 3q28 is Associated with Gastric Cancer Risk via Modifying its Regulation by MicroRNA-140

Lu¹,

Yang²,

Ma³

2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: TP63 was believed to play an important role in the development of many malignancies, while the polymorphisms located at the miRNA binding sites within the 3’UTR of TP63 mRNA may interfere with its expression. In this study, we aimed to study the role of TP63 regulation in the tumorigenesis of gastric cancer (GC). Methods: Computational and luciferase analysis were used to search and confirm the target of miR-140. Real-time PCR, western-blot, MTT assay, and flow cytometry cell cycle analysis were utilized to explore the molecular pathway of miR-140 involved in the progression of GC. Results: TP63 was identified as a direct target gene of miR-140. In HT-29 cells over-expressing miR-140, the luciferase activity was decreased when the cells were transfected with wild-type TP63 3’UTR, but remained unchanged when the cells were transfected with mutant 1 and mutant 2 TP63 3’UTR. In addition, the level of TP63 in HT-29 cells transfected with miR-140 mimic was evidently down-regulated, whereas the level of TP63 in HT-29 cells transfected with miR-140 inhibitor was significantly up-regulated. Furthermore, based on the results from MTT assay and flow cytometry cell cycle analysis, HT-29 cells transfected with miR-140 mimics were associated with significantly higher viability compared to the cells transfected with the control plasmid, suggesting that an increased expression of miR-140 protected HT-29 cells against apoptosis. Finally, when miR-140 expression was high, the number of cells at the G1 phase was notably increased, accompanied by a remarkably diminished number of cells at the S phase. Conclusions: The rs35592567 polymorphism in TP63 affected the expression of TP63 by interfering with its interaction with miR-140, and could serve as an explanation for the increased risk of GC.

show abstract

microRNAs: Small molecules with a large impact on colorectal cancer

Moazzendizaji

Севбитов

Ezzatifar

et al. 2021

Biotech and App Biochem

View full text Add to dashboard Cite

Colorectal cancer (CRC) accounts for one of the main cancer‐related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF‐β pathways, was clarified.

show abstract

Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy

Cited by 123 publications

References 55 publications

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

A functional Variant (Rs35592567) in TP63 at 3q28 is Associated with Gastric Cancer Risk via Modifying its Regulation by MicroRNA-140

microRNAs: Small molecules with a large impact on colorectal cancer

Contact Info

Product

Resources

About