The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

Jaca, Anelisa; Govender, Padmini; Locketz, Michael; Naidoo, Richard

doi:10.1136/jclinpath-2016-204031

Cited by 35 publications

(18 citation statements)

References 28 publications

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“…Some miRNAs have been observed to be dysregulated in CRC tissues (35). The function of miRNAs in CRC involves controlling EMT (36) and affecting cell proliferation, migration and invasion (37), similar to the function of lncRNAs in CRC. In ovarian cancer, the miRNA-lncRNA signature is important in patient survival (38).…”

Section: Discussionmentioning

confidence: 96%

Long non‑coding RNA 00152 functions as a competing endogenous RNA to regulate NRP1 expression by sponging with miRNA‑206 in colorectal cancer

et al. 2018

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Colorectal cancer (CRC) is the third most common type of cancer; however, the molecular mechanisms underlying colorectal tumor metastasis and growth remain elusive. Recently, accumulating evidence has indicated that long non‑coding RNAs (lncRNAs) play a critical role in CRC progression and metastasis; however, the biological role and clinical significance of lncRNA 00152 (lnc00152) in CRC remains largely unknown. Thus, in this study, lnc00152 expression was measured in 80 human CRC tissue samples, 40 non‑cancerous tissue samples, and 3 CRC cell lines (SW480, SW620 and LoVo) using RT‑qPCR. We examined the effects of lnc00152 on CRC cells following transfection with lnc00152 overexpression plasmid or respective siRNA in vitro and in vivo. Luciferase assays revealed the mechanism driving competitive endogenous RNA (ceRNA). We identified that lnc00152 was aberrantly overexpressed in colorectal tumors and cancer cells and that lnc00152 was modulated by miRNA‑206. lnc00152 overexpression enhanced the proliferative and invasive ability of CRC cells in vitro, promoted tumor growth in vivo, and was associated with the shorter overall survival of patients with CRC. In addition, lnc00152 overexpression promoted epithelial-mesenchymal transition (EMT) and increased neuropilin‑1 (NRP1) expression in the CRC cells. By contrast, lnc00152 silencing exerted a counteractive effect. Collectively, these findings demonstrate the critical role of lnc00152 in tumor growth and progression in CRC, and identify a novel therapeutic target associated with CRC development and progression.

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Section: Discussionmentioning

confidence: 96%

Long non‑coding RNA 00152 functions as a competing endogenous RNA to regulate NRP1 expression by sponging with miRNA‑206 in colorectal cancer

et al. 2018

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“…Previous studies reported that the overexpression of miR‐21 is associated with the invasion and metastasis of various human cancer cells . Therefore, in order to determine whether miR‐21‐3p was necessary for cell invasion and migration, transwell assay and wound healing assay were performed to detect the invasive as well as migratory abilities of the HCT116 cells, respectively, following transfection with miR‐21‐3p inhibitors or NC‐miRNA.…”

Section: Resultsmentioning

confidence: 99%

“…Although accumulating evidence supports miR‐21‐5p as 1 mature miR‐21 strand that is overexpressed in many cancers, and plays a role in the processes of carcinogenesis and metastasis, studies regarding the biological role of the other miR‐21 passenger strand, miR‐21‐3p, in CRC cells are limited. The comprehensive understanding of CRC at molecular and cellular levels is still urgently needed to help reduce the incidence and to improve the survival rate of CRC patients.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of microRNA‐21‐3p suppresses proliferation as well as invasion and induces apoptosis by targeting RNA‐binding protein with multiple splicing through Smad4/extra cellular signal‐regulated protein kinase signalling pathway in human colorectal cancer HCT116 cells

Hou

Guo

Zhao

et al. 2018

Clin Exp Pharma Physio

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MicroRNA-21-3p (miR-21-3p), the passenger strand of pre-mir-21, has been found to be high-expressing in various cancers and to be associated with tumour malignancy, which is proposed as a novel focus in malignant tumours. Colorectal cancer (CRC), currently known as one of the most prevalent malignancy, is a leading cause of cancer death. This study aimed to investigate the key role of miR-21-3p in CRC by inhibiting its expression using transfection with miR-21-3p inhibitors into human CRC HCT116 cells. Results showed that the expression of miR-21-3p was higher than other CRC cells used in the study including Lovo, HT29, Colo320 and SW480 cells, inhibition of which suppressed the proliferation and induced cell cycle arrest in HCT116 cells. Besides, transfection with miR-21-3p inhibitors also attenuated cell migration and invasion, and induced apoptosis as well. Moreover, luciferase assay confirmed RBPMS as a direct target of miR-21-3p in HCT116 cells. Further, miR-21-3p inhibitors increased the nuclear accumulation of Smad4 and reduced phosphorylation of ERK. Interestingly, we found that silence of RBPMS using RNA interference (siRNA) not only elevated the cell viability but also increased the phosphorylation of ERK and reversed the nuclear accumulation of Smad4 induced by miR-21-3p inhibitors in HCT116 cells. Data suggest that inhibition of miR-21-3p suppresses cell proliferation, invasion as well as migration and induces apoptosis by directly targeting RBPMS through Smad4/ERK signalling pathway in HCT116 cells. Our study demonstrates miR-21-3p as a potent target for suppressing tumour progression of CRC which may have implications in CRC therapy in the future.

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“…Additionally, an in vitro assay involving Transwell plates revealed that miR-650 promotes HCC cell migration and invasion. There is accumulating evidence that miRNAs have a crucial function related to the progression of HCC EMT [19,20]. Considering the EMT is a wellknown basal mechanism related to cancer cell migration and invasion [3], we speculated that miR-650 may influence HCC EMT.…”

Section: Discussionmentioning

confidence: 97%

miR-650 Promotes the Metastasis and Epithelial–Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression

Han

Yin

Zhang³

2018

Cell Physiol Biochem

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Background/Aims: Previous studies have confirmed that microRNAs are involved in the metastasis and epithelial–mesenchymal transition (EMT) of malignancies. In this study, we examined whether miR-650 promotes the migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells by targeting the large tumor suppressor kinase 2 gene (LATS2). Methods: qRT-PCR was used to detect expression of miR-650 in HCC tissues and paired normal tissues. MTT and Transwell assay were used to observe the effect of miR-650 on proliferation, migration and invasion of HCC cells. Western blot assay and Immunohistochemistry were performed to demonstrate association between miR-650 expression level and epithelial-mesenchymal transition (EMT) related protein. Mechanistically, Reporter luciferase assay was performed to reveal whether large tumor suppressor kinase 2 (LATS2) was a direct target of miR-650 in HCC cells. Results: We observed that miR-650 levels were largely up-regulated in HCC tissues, and that the increased expression was closely associated with the adverse clinical features of HCC patients. Additionally, the expression of LATS2, which was identified as a direct target of miR-650, can counteract the effects of miR-650 in HCC. Furthermore, we demonstrated that high miR-650 expression levels and low LATS2 expression levels in tumors may indicate a poor prognosis for HCC patients. Conclusion: In conclusion, the miR-650/LATS2 pathway may serve as a novel prognostic biomarker and an attractive therapeutic target for HCC patients.

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The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

Abstract: Our data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.

Cited by 35 publications

References 28 publications

Long non‑coding RNA 00152 functions as a competing endogenous RNA to regulate NRP1 expression by sponging with miRNA‑206 in colorectal cancer

Long non‑coding RNA 00152 functions as a competing endogenous RNA to regulate NRP1 expression by sponging with miRNA‑206 in colorectal cancer

Inhibition of microRNA‐21‐3p suppresses proliferation as well as invasion and induces apoptosis by targeting RNA‐binding protein with multiple splicing through Smad4/extra cellular signal‐regulated protein kinase signalling pathway in human colorectal cancer HCT116 cells

miR-650 Promotes the Metastasis and Epithelial–Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression

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