Upregulation of miR-542-3p inhibits the growth and invasion of human colon cancer cells through PI3K/AKT/survivin signaling

Yang, Chuang; Wang, Minghuan; Zhou, Jianqiu; Chi, Qiang

doi:10.3892/or.2017.6054

Cited by 17 publications

(16 citation statements)

References 24 publications

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“…miR-495 induces cell proliferation, invasion, and migration in both gastric 49 and bladder cancers, 50 but an opposite effect was observed in colorectal cancer 51 . Both miR-539 and miR-542-3p have been shown to have an oncosuppressive function in several cancers,52, 53, 54, 55 although their role is still poorly explored and, specifically, their function in MM has not been investigated. Even less defined is the role of miR-518f, which was found to be, together with 28 other miRNAs, significantly downregulated in an in vitro -selected highly invasive endometrial cancer cell line 56 .…”

Section: Resultsmentioning

confidence: 99%

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma

Misso

Zarone

Lombardi

et al. 2019

Molecular Therapy - Nucleic Acids

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miR-125b, ubiquitously expressed and frequently dysregulated in several tumors, has gained special interest in the field of cancer research, displaying either oncogenic or oncosuppressor potential based on tumor type. We have previously demonstrated its tumor-suppressive role in multiple myeloma (MM), but the analysis of molecular mechanisms needs additional investigation. The purpose of this study was to explore the effects of miR-125b and its chemically modified analogs in modulating cell viability and cancer-associated molecular pathways, also focusing on the functional aspects of stress adaptation (autophagy and senescence), as well as programmed cell death (apoptosis). Based on the well-known low microRNA (miRNA) stability in therapeutic application, we designed chemically modified miR-125b mimics, laying the bases for their subsequent investigation in in vivo models. Our study clearly confirmed an oncosuppressive function depending on the repression of multiple targets, and it allowed the identification, for the first time, of miR-125b-dependent miR-34a stimulation as a possible consequence of the inhibitory role on the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3)/miR-34a feedback loop. Moreover, we identified a pattern of miR-125b-co-regulated miRNAs, shedding light on possible new players of anti-MM activity. Finally, functional studies also revealed a sequential activation of senescence, autophagy, and apoptosis, thus indicating, for the first two processes, an early cytoprotective and inhibitory role from apoptosis activation.

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Section: Resultsmentioning

confidence: 99%

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma

Misso

Zarone

Lombardi

et al. 2019

Molecular Therapy - Nucleic Acids

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“…33 It has been reported that LY294002, which acts on colon cancer cells and ovarian cancer cells, could specifically inhibit PI3K, reduce the expression of phosphorylated Akt, and then block the PI3K/Akt signaling pathway, thereby significantly inhibiting cell growth and inducing apoptosis. 34,35 FOXO3A is a functional protein of Akt protein that regulates cell growth and migration. 36 Studies have also shown that FOXO3A, as a tumor-suppressor gene, could induce the expressions of pro-apoptotic genes.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

et al. 2019

Cancer Biology & Therapy

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The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression.

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“…Since miR-542-3p functions as a tumor suppressor in human cancers [ 50 , 51 ], its antitumor activity has been evaluated in bladder cancer, colorectal cancer, hepatocellular carcinoma, and melanoma. Some of the studies also found that miR-542-3p targeted Survivin to exert antitumor effects [ 52 , 53 ]. Interestingly, combinations of the Survivin inhibitor (YM155) and miR-542-3p more potently promoted apoptosis of colon cancer cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some of the studies also found that miR-542-3p targeted Survivin to exert antitumor effects [ 52 , 53 ]. Interestingly, combinations of the Survivin inhibitor (YM155) and miR-542-3p more potently promoted apoptosis of colon cancer cells [ 52 ]. In addition, miR-542-3p inhibited tumor growth, cancer cell migration and invasion, and/or metastasis by targeting cortactin ( CTTN ) or OTUB1 in colorectal cancer cells [ 54 , 55 ], the serine/threonine protein kinase, PIM1 in melanoma [ 56 ], and FZD7/Wnt signaling in hepatocellular cancer cells [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Survivin-targeting miR-542-3p overcomes HER3 signaling-induced chemoresistance and enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer

et al. 2018

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Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation. Here we showed that overexpression and specific knockdown of HER3 reduced and enhanced expression of two Survivin-targeting miRNAs, miR-203 and miR-542-3p, in breast cancer cells, respectively. While the specific inhibitor of either miR-203 or miR-542-3p attenuated an anti-HER3 antibody-induced downregulation of Survivin, inhibition of miR-542-3p exhibited a better efficacy than miR-203 inhibition did. Consistently, miR-542-3p mimic was much more effective than miR-203 mimic not only in inhibition of Survivin, but also in enhancement of paclitaxel-induced apoptosis in HER2-overexpressing breast cancer cells. Moreover, the combination of miR-542-3p mimic and paclitaxel, as compared with either agent alone, significantly inhibited in vivo tumor growth of HER2-overexpressing breast cancer cells. Collectively, our data indicated that the HER3/PI-3K/Akt signaling upregulates Survivin via suppression of miR-203 and miR-542-3p. Because miR-542-3p has three binding sites on the 3′-UTR of Survivin mRNA, its mimic was able to effectively downregulate Survivin in vitro and in vivo. Thus, miR-542-3p-replacement therapy is an excellent approach to overcome HER3-mediated paclitaxel resistance and significantly enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer.

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Upregulation of miR-542-3p inhibits the growth and invasion of human colon cancer cells through PI3K/AKT/survivin signaling

Cited by 17 publications

References 24 publications

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

Survivin-targeting miR-542-3p overcomes HER3 signaling-induced chemoresistance and enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer

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