MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression

Yang, Juan; Li, Guiyuan; Zhang, Keqiang

doi:10.1016/j.biopha.2015.12.027

Cited by 35 publications

(31 citation statements)

References 37 publications

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“…It has been demonstrated that miRNAs are aberrantly expressed in various cancers such as lung cancer, liver cancer, and gastric cancer . MicroRNA‐125a (MiR‐125a), located on chromosome 19q13, is a member of the miR‐125 family and has been reported as a potential tumor suppressor in multiple cancers by targeting different genes, such as osteosarcoma, ovarian cancer, breast cancer, lung cancer, and glioma . However, little is known about the expression profile and functional roles of miR‐125a in RCC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells

Sun

Guo

Yao

et al. 2018

J of Cellular Biochemistry

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Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA-125a (miR-125a) has been demonstrated to be implicated in various cancers. However, the functional role of miR-125a in RCC remains largely unclear. This study was aimed to investigate the functional role of miR-125a and the expression relevance of signal transducers and activators of transcription 3 (STAT3) with hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR-125a was downexpressed in 786-O cells, and examined transfected efficiency. According to functional assay, overexpression of miR-125a inhibited cell migration and cell invasion, but no obvious effect was observed on cell proliferation. The luciferase activity assay showed that miR-125a could directly target STAT3 3'-untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR) assay and Western blot analysis demonstrated that miR-125a could inhibit STAT3 expression at both messenger RNA and protein levels. Furthermore, the combination sites between STAT3 and HAS1 were predicted by prediction of transcription factor binding sites database analysis. The expression of STAT3 was correlated with HAS1 expression, exemplified by the same tendency detected by qPCR assay. Taken together, our results preliminarily demonstrate that miR-125a could constrain cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting STAT3. It is likely to facilitate a better understanding of the regulation mechanisms of miR-125a in RCC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells

Sun

Guo

Yao

et al. 2018

J of Cellular Biochemistry

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“…The expression of GALNT14 appeared to be a better predictor of TRAIL sensitivity. It has been suggested that verifying the expression of GALNT14 may be used as a strategy to clarify patients who are more likely to benefit from chemotherapy [40, 41]. Here, we demonstrated that GALNT14 was regulated by Osx and was at least partly responsible for the decrease in chemosensitivity caused by Osx in breast cancer cells.…”

Section: Discussionmentioning

confidence: 49%

“…Studies have shown that O-glycosylation and GALNT members play critical roles in various biological processes as well as in human disease development, including tumourigenesis [18]. For example, GALNT3 serves as an unfavourable prognostic marker in non-small cell lung cancer [19].…”

Section: Introductionmentioning

confidence: 99%

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

Chen

Bao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. Methods: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. Results: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. Conclusion: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

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“…A, Schematic diagram of predicted binding sites in 3′-UTR of USP5. [39][40][41] In this study, by investigating the mechanism of miR-125a in the proliferation and apoptosis of MM cells, it was found that miR-125a could suppress the proliferation of MM cells and promote the apoptosis of MM cells by targeting the expression of USP5, which would provide a certain theoretical basis for the gene-targeted therapy of MM. C, Determination of the mRNA expression levels of USP5 in miR-125a mimic or control transfected U266 and NCI-H929 cells by qRT-PCR.…”

Section: Discussionmentioning

confidence: 95%

miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

Wu¹,

Zhang²,

Chen³

et al. 2019

J of Cellular Biochemistry

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miR‐125a is a microRNA that is frequently diminished in various human malignancies. However, the mechanism by which impaired miR‐125a promotes cancer growth remains undefined. In this study, we investigated the role of miR‐125a in the proliferation and apoptosis of multiple myeloma (MM). To do this, we used MM tissue samples (from 40 anonymous patients), normal matched control samples, and five MM‐derived cell lines. We also established a mouse model of MM xenograft to explore the effect of overexpression of miR‐125a on the MM growth in vivo. Quantitative real‐time polymerase chain reaction revealed that the miR‐125a expression was broadly reduced in MM tissues and cell lines. The impairment of miR‐125a in MM tissues was functionally relevant because the overexpression of miR‐125a remarkably decreased the cell viability and colony‐forming activity, at least in part, by promoting apoptosis in two miR‐125a‐deficient MM cell lines: NCI‐H929 and U266. Interestingly, we also discovered that the human gene encoding the ubiquitin‐specific peptidase 5 (USP5), which is known to promote cellular deubiquitination and ubiquitin/proteasome‐dependent proteolysis, was a direct transcriptional target for miR‐125a to repress. More importantly, the heterologous expression of USP5 significantly reversed the growth‐inhibitory effects of miR‐125a on MM cells in vitro. In the mouse xenograft model, overexpressed miR‐125a prominently inhibited the growth of MM tumors and concomitantly reduced the expression of USP5 in tumor tissues. These results suggest that miR‐125a inhibits the expression of USP5, thereby mitigating the proliferation and survival of malignant MM cells. We propose that USP5 acts as an oncoprotein in miR‐125a‐missing cancers.

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MiR-125a regulates ovarian cancer proliferation and invasion by repressing GALNT14 expression

Cited by 35 publications

References 37 publications

MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells

MicroRNA‐125a suppresses cell migration, invasion, and regulates hyaluronic acid synthase 1 expression by targeting signal transducers and activators of transcription 3 in renal cell carcinoma cells

Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

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