MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1 in endometrial cancer

Wang, Zhen; Wang, Wei; Huang, Kangrong; Wang, Yueling; Li, Jing; Yang, Xinyuan

doi:10.18632/oncotarget.22770

Cited by 39 publications

(30 citation statements)

References 38 publications

(27 reference statements)

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“…Of the four discriminating miRNAs between EEC and SEC identified in this study, only miR-34a-5p has been studied extensively. In non-selective EC, a decreased miR-34a-5p level was reported to associate with higher stage and metastasis [ 43 , 44 ], whereas another study revealed that miR-34a-5p targets SNAIL and other genes such as those involved in epithelial-mesenchymal transition (EMT) [ 45 ]. In another study, decreased miR-34a-5p expression upregulated the L1CAM level in EC cell lines and tumours [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Discriminating miRNA Profiles between Endometrioid Well- and Poorly-Differentiated Tumours and Endometrioid and Serous Subtypes of Endometrial Cancers

Kalinkova

Kajo

Karhánek

et al. 2020

IJMS

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The discrimination of different subtypes of endometrial carcinoma (EC) is frequently problematic when using the current histomorphological classification; therefore, new markers for this differentiation are needed. Here, we examined differences in miRNA expression between well- and poorly-differentiated (grades 1 and 3) endometrioid endometrial carcinoma (EEC) and between EEC and serous endometrial carcinoma (SEC). The expression of 84 tumour-suppressor miRNAs was analysed by real-time polymerase chain reactions in 62 EC and 20 non-neoplastic endometrial specimens. The potential functions of the differentially expressed miRNAs were determined by bioinformatics analyses. The expression of let-7c-5p, miR-125b-5p, miR-23b-3p, and miR-99a-5p in grade 3 EEC was decreased compared to grade 1 EEC. To discriminate between EEC and SEC, let-7g-5p, miR-195-5p, miR-34a-5p, and miR-497-5p expression was significantly downregulated in SEC. In bioinformatic analyses, miRNAs that could discriminate grade 1 from grade 3 mainly targeted genes involved in PI3K-AKT signaling, whereas miRNAs that could discriminate EEC from SEC targeted genes involved in several signaling pathways, but mainly MAPK signaling. Taken collectively, our results indicate that the activation of certain signaling pathways can be useful in the molecular characterization of EEC and SEC.

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Section: Discussionmentioning

confidence: 99%

Discriminating miRNA Profiles between Endometrioid Well- and Poorly-Differentiated Tumours and Endometrioid and Serous Subtypes of Endometrial Cancers

Kalinkova

Kajo

Karhánek

et al. 2020

IJMS

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“…miR-34a and miR-424 are reduced and thought to be tumor suppressors in EC [ 21 , 22 ]. Consistent with these studies, we found low levels of miR-34a and miR-424 in EC cell lines and EC patient tissues, and these low expressions correlated with a poorer prognosis in EC.…”

Section: Discussionmentioning

confidence: 99%

miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation

et al. 2018

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Although the oncogene MMSET (also known as NSD2 or WHSC1) has an essential role in malignancies, its impact on human endometrial cancer (EC) metastasis and the molecular mechanism of MMSET regulation are largely unknown. We report that MMSET was markedly upregulated in EC cell lines and EC tissues, and was significantly associated with poor survival in EC. MMSET overexpression greatly promoted EC cell invasion and sphere formation, whereas inhibition of MMSET reduced EC cell invasion and sphere formation. Importantly, Twist1 was required for MMSET-induced EC cell invasion and sphere formation. Moreover, we demonstrate that miR-34a, miR-424 and miR-513 directly modulate MMSET expression to attenuate the invasion and sphere formation capacity of EC cells. miR-34a, miR-424 and miR-513 were down-regulated in EC compared with normal tissue, and reduced expression of miR-34a, miR-424 and miR-513 was clinically associated with a poorer prognosis in EC patients. Furthermore, specific inhibition of MMET with BIX-01294 led to decreased EC cell invasion and impaired sphere formation. These findings suggest a pro-metastatic role for MMSET in EC and reveal that the repression of miR-34a, miR-424 and miR-513 contributes to the overexpression of MMSET during EC metastasis.

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“…A large number of studies suggest that miRNAs are closely associated with tumorigenesis. Additionally, miRNAs are demonstrated to regulate tumor cell proliferation, migration and invasion by suppressing target gene expression post-transcriptionally ( 27 ). Abnormal expression of miRNAs is frequently observed in types of cancer, including breast cancer ( 28 ), colorectal cancer ( 29 ), non-small cell lung cancer ( 30 ) and hepatocellular carcinoma ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA FEZF1‑AS1 contributes to cell proliferation, migration and invasion by sponging miR‑4443 in hepatocellular carcinoma

et al. 2018

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As one of the most common and aggressive cancer types, hepatocellular carcinoma (HCC) leads to a large number of fatalities every year. However, the pathogenesis of HCC remains largely unknown. In the present study, it was identified that FEZF1-AS1 was significantly upregulated in HCC cell lines and tissues, as determined by reverse transcription-quantitative polymerase chain reaction. Additionally, it was observed that higher expression of FEZF1-AS1 in patients with HCC indicated poorer prognosis. Furthermore, it was identified that knockdown of FEZF1-AS1 markedly inhibited the proliferation, colony formation, migration and invasion of Hep3B and Huh7 cells, as determined by Cell Counting Kit-8, colony formation and Transwell assays. In terms of mechanism, it was observed that FEZF1-AS1 acted as a sponge for microRNA (miR)-4443. The results of a luciferase reporter assay revealed that overexpression of miR-4443 significantly inhibited the luciferase activity in Hep3B and Huh7 cells. Additionally, miR-4443 overexpression markedly inhibited the expression of FEZF1-AS1, and vice versa. It was additionally identified that miR-4443 was downregulated in HCC tissues. There was an inverse correlation between the expression of miR-4443 and FEZF1-AS1 in HCC tissues. Furthermore, through functional experiments, it was identified that knockdown of FEZF1-AS1 significantly inhibited the proliferation, migration and invasion of HCC cells, whereas inhibition of miR-4443 reversed these effects. Collectively, the present results demonstrated that FEZF1-AS1 acts as an oncogene by acting as a sponge for miR-4443.

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MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1 in endometrial cancer

Cited by 39 publications

References 38 publications

Discriminating miRNA Profiles between Endometrioid Well- and Poorly-Differentiated Tumours and Endometrioid and Serous Subtypes of Endometrial Cancers

Discriminating miRNA Profiles between Endometrioid Well- and Poorly-Differentiated Tumours and Endometrioid and Serous Subtypes of Endometrial Cancers

miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation

lncRNA FEZF1‑AS1 contributes to cell proliferation, migration and invasion by sponging miR‑4443 in hepatocellular carcinoma

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