Therapeutic Inhibition of miR-4260 Suppresses Colorectal Cancer via Targeting MCC and SMAD4

Xiao, Junjie; Lv, Dongchao; Zhou, Jinzhe; Bei, Yihua; Chen, Ting; Hu, Muren; Zhou, Qing; Fu, Siyi; Huang, Qi

doi:10.7150/thno.19168

Cited by 39 publications

(27 citation statements)

References 35 publications

(48 reference statements)

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“…Given its prevalence, it is vital that current understanding of the development and progression of CRC be improved [13,14]. Recent research has highlighted the close relationship between altered miRNA expression and the growth, metastasis, and angiogenic development of CRC [15,16]. As such, efforts to better understand the miRNAs which promote or suppress CRC progression may offer invaluable diagnostic and/or therapeutic opportunities.…”

Section: Discussionmentioning

confidence: 99%

miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells

Hong¹,

Cheng²,

Zheng³

et al. 2020

J. Cancer

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Purpose: MicroRNAs (miRNAs) are key regulators of the growth and development of a wide range of cancer types such as colorectal cancer (CRC). A number of previously studies have observed that the levels of miR-365a-3p expression are dysregulated in many cancers, but the specific role of this miRNA in CRC and its association with patient prognosis remains unclear. Methods: The expression of miR-365a-3p in CRC tissues and cell lines was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between miR-365a-3p expression and clinicopathological characteristics was further analyzed. After increasing the expression of miR-365a-3p by plasmid transfection in CRC cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among miR-365a-3p, ADAM10 and JAK in CRC, was explored by luciferase reporter assay. Results: In the present study, we determined that CRC cells and clinical samples exhibited decreased miR-365a-3p expression, and this was associated with larger tumor size, lymph node metastasis, and local invasion. Patients with lower expression of miR-365a-3p had significantly decreased recurrence-free survival (RFS) and overall survival (OS) relative to those with higher levels of this miRNA. In a multivariate analysis, we confirmed that reduced miR-365a-3p levels were independently predictive of poorer CRC patient outcomes. In a functional study, we determined that elevated miR-365a-3p expression inhibited the ability of CRC cells to proliferate and metastasize in vitro and in vivo. We further identified ADAM10 as a direct miR-365a-3p target, resulting in the suppression of ADAM10 expression in cells expressing this miRNA and ADAM10 levels were in turn closely linked to JAK/STAT signaling. Conclusion: Our study suggested the ability of miR-365a-3p to inhibit the progression of CRC at least in part via suppressing ADAM10 expression and associated JAK/STAT signaling, thus identifying this signaling axis as a possible prognostic and therapeutic target in CRC.

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Section: Discussionmentioning

confidence: 99%

miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells

Hong¹,

Cheng²,

Zheng³

et al. 2020

J. Cancer

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“…Accumulative evidence indicates that miRNAs serve as oncogenes or tumour suppressors that act as pivotal players in tumourigenesis and tumour progression. Additionally, deregulation of miRNAs has been observed in various cancers, including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer 22 – 25 . Numerous studies have examined the expression profiles of miRNAs to explore the mechanism of miRNA actions in tumourigenesis and tumour progression.…”

Section: Discussionmentioning

confidence: 99%

miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma

Jin

et al. 2018

Cell Death Dis

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Gallbladder cancer (GBC) is the most common malignant tumour of the biliary track system. Angiogenesis plays a pivotal role in the development and progression of malignant tumours. miR-143-3p acts as a tumour suppressor in various cancers. Their role in GBC is however less well defined. Here we show that the expression levels of miR-143-3p were decreased in human GBC tissues compared with the non-tumour adjacent tissue (NAT) counterparts and were closely associated with overall survival. We discovered that miR-143-3p was a novel inhibitor of tumour growth and angiogenesis in vivo and in vitro. Our antibody array, ELISA and PLGF rescue analyses indicated that PLGF played an essential role in the antiangiogenic effect of miR-143-3p. Furthermore, we used miRNA target-prediction software and dual-luciferase assays to confirm that integrin α6 (ITGA6) acted as a direct target of miR-143-3p. Our ELISA and western blot analyses confirmed that the expression of PLGF was decreased via the ITGA6/PI3K/AKT pathway. In conclusion, miR-143-3p suppresses tumour angiogenesis and growth of GBC through the ITGA6/PI3K/AKT/PLGF pathways and may be a novel molecular therapeutic target for GBC.

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“…Aberrant expression of miRNAs has been acknowledged to be involved in initiation and development of CRC. For example, miR-4260 plays a promotive role in CRC by targeting MCC and SMAD4 [39].…”

Section: Discussionmentioning

confidence: 99%

MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4

Chang

Sun

Zhang

et al. 2020

Preprint

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Background MicroRNAs are a class of small non-coding RNAs which act as oncogenes or tumor suppressors through targeting specific mRNAs. MiR-3622a-3p is found to be decreased in colorectal cancer (CRC) in TCGA database and there are few reports about the role of miR-3622a-3p in cancers. Our research aimed to explore the effect of miR-3622a-3p in CRC. Methods MiR-3622a-3p expression in CRC tissues and cells was examined by qRT-PCR. The effect of miR-3622a-3p on proliferation, apoptosis, cell cycle, migration and invasion of CRC cells were investigated by a serious of biological function assays. We performed dual luciferase assay to confirm the interaction between miR-3622a-3p and its potential target gene. Western blot was carried out to determine the effect of miR-3622a-3p on stemness features and EMT. Tumor xenograft model and in vivo metastasis model were established using nude mice. The CRC organoid model was constructed with fresh CRC tissues. Results MiR-3622a-3p was down-regulated in CRC tissues and cells. Biological function assays revealed that miR-3622a-3p could inhibit the malignant biological properties of CRC. MiR-3622a-3p suppressed stemness features and EMT of CRC cells by SALL4 mRNA degradation. The results of animal experiments showed miR-3622a-3p could inhibit CRC cell proliferation and metastasis in vivo . The growth of organoids was also suppressed by miR-3622a-3p. Conclusions Taken together, the results of our study indicate miR-3622a-3p exerts antioncogenic role in CRC by downregulation of SALL4. The research on miR-3622a-3p might provide a new insight into treatment of CRC.

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Therapeutic Inhibition of miR-4260 Suppresses Colorectal Cancer via Targeting MCC and SMAD4

Cited by 39 publications

References 35 publications

miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells

miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells

miR-143-3p targeting of ITGA6 suppresses tumour growth and angiogenesis by downregulating PLGF expression via the PI3K/AKT pathway in gallbladder carcinoma

MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4

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