miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells

Li, Yong; Gong, Ping; Hou, Jixue; Huang, Wei; Ma, Xiaoping; Wang, Yuli; Li, Jing; Cui, Xiaobin; Li, Na

doi:10.1155/2018/7498514

Cited by 24 publications

(18 citation statements)

References 51 publications

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“…qRT-PCR assay showed that overexpression of miR-154 and miR-34a suppressed circDENND2A levels ( Figure 5A). Previous reports revealed that miR-34a was a tumor inhibitor and that its expression was weak in numerous cancers (Li et al, 2018;Haghi et al, 2019;Luo et al, 2019). Our data verified that miR-34a level was down-regulated in NSCLC tissues (Figure 5B).…”

Section: Circdennd2a Sponged Mir-34a and Induced Ccne1 Expressionsupporting

confidence: 88%

CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling

et al. 2020

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The mechanism regulating non-small cell lung cancers (NSCLCs) is unclear. In this study, we aimed to determine the roles of DENN domain containing 2A (circDENND2A) in the progression of NSCLC. Circular RNAs (circRNAs) are composited by "head to tail" splicing of coding or non-coding RNAs (ncRNAs), whose crucial roles in human cancers had been revealed. CircDENND2A, a new circRNA, was revealed to induce cell proliferation and migration. Our data indicated that circDENND2A was a probable oncogene in human cancers. However, the roles of circDENND2A in NSCLC remained unknown. Here, we demonstrated that circDENND2A was down-regulated in NSCLC samples. Loss-of-function assays showed circDENND2A knockdown suppressed cell growth via inducing cell cycle arrest and apoptosis and inhibited cell migration and invasion. Bioinformatics analysis and competing endogenous RNA (ceRNA) network analysis revealed that circDENND2A was involved in regulating cell cycle and tumor protein p53 (TP53) signaling via miR-34a/CCNE1 (cyclin E1). Further validation showed that circDENND2A could directly bind to miR-34a, promoting CCNE1 expression in NSCLC. In addition, rescue assays demonstrated that restoration of CCNE1 significantly impaired the suppressive effects of circDENND2A silencing in terms of NSCLC growth, migration, and invasion. We thought this study indicated that circDENND2A/miR-34a/CCNE1 may be a potential therapeutic target for NSCLC.

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Section: Circdennd2a Sponged Mir-34a and Induced Ccne1 Expressionsupporting

confidence: 88%

CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling

et al. 2020

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“…For example, in the 5-FU-resistant cell line DLD-1/5-FU, mature miR-34a transfection attenuated 5-FU resistance and inhibited growth in the parental cells 38. MiR-34a decreased multidrug resistance and inhibited migration and invasion in colon cancer cells 39,40. However, in several studies, miR-34a has also been shown to function by enhancing chemoresistance 37.…”

Section: Discussionmentioning

confidence: 99%

<p>lncRNA KCNQ1OT1 enhances the chemoresistance of oxaliplatin in colon cancer by targeting the miR-34a/ATG4B pathway</p>

Li¹,

Li²,

Li³

et al. 2019

OTT

104

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Purpose The chemoresistance of colon cancer to oxaliplatin (L-OHP) indicates poor prognosis. Long non-coding RNA (lncRNA) KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) has been shown to participate in the tumorigenesis of several types of cancers. However, little is known about the role of KCNQ1OT1 in the chemoresistance and prognosis of colon cancer. Materials and methods Quantitative-PCR and Western blot were used to measure the expression profiles of KCNQ1OT1, miR-34a, and Atg4B in colon cancer tissues and cells. Cell viability assay and flow cytometry were used to examine their effects on cell proliferation and death. Cleavage of LC3 and GFP-LC3 plasmid transfection were used to detect autophagic activity. Double luciferase reporter assay was used to verify the interactions between miRNA and lncRNA or mRNA. Xenograft tumor model was used to verify the effects of KCNQ1OT1 in vivo. Results In this study, it is shown that the expression level of KCNQ1OT1 was increased in tumor, which indicated poor prognosis in colon cancer patients. Using colon cancer cell lines HCT116 and SW480, it was demonstrated that knockdown of KCNQ1OT1 decreased the cell viability and increased the apoptosis rates upon L-OHP treatment. Further studies indicated that Atg4B upregulation was partially responsible for KCNQ1OT1-induced protective autophagy and chemoresistance. Moreover, miR-34a functioned as a bridge between KCNQ1OT1 and Atg4B, which could be sponged by KCNQ1OT1, while it could also bind to the 3′-UTR of Atg4B and downregulate its expressions. Finally, we show that the KCNQ1OT1/miR-34a/Atg4B axis regulated the chemoresistance of colon cancer cells in vitro and in vivo. Conclusion lncRNA KCNQ1OT1 promoted the chemoresistance of colon cancer by sponging miR-34a, thus upregulating the expressions of Atg4B and enhancing protective autophagy. KCNQ1OT1 might become a promising target for colon cancer therapeutics.

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“…MiR-34a is a tumor suppressor miRNA: In colorectal cancer its expression is usually downregulated, often because of TGF-β action or long non-coding RNA acting as sponge for the miRNA [195,196]. Key features of miR-34a are the inhibition of cell migration and its chemosensitizer role in colorectal cancer [197,198]. COUP-TFII directly induces the expression of miR-21 in TGF-β-treated cells, resulting in the downregulation of SMAD7 whereas it reduces miR-34a [161,162]; hence, modulating miR-21a and miR-34a, COUP-TFII strengthen its action as tumor oncogene and induces EMT in colorectal cancer.…”

Section: The Gastrointestinal Cancers: Mostly An Oncogenementioning

confidence: 99%

COUP-TFII in Health and Disease

Polvani

Pepe

Milani

et al. 2019

Cells

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The nuclear receptors (NRs) belong to a vast family of evolutionary conserved proteins acting as ligand-activated transcription factors. Functionally, NRs are essential in embryogenesis and organogenesis and in adulthood they are involved in almost every physiological and pathological process. Our knowledge of NRs action has greatly improved in recent years, demonstrating that both their expression and activity are tightly regulated by a network of signaling pathways, miRNA and reciprocal interactions. The Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII, NR2F2) is a NR classified as an orphan due to the lack of a known natural ligand. Although its expression peaks during development, and then decreases considerably, in adult tissues, COUP-TFII is an important regulator of differentiation and it is variably implicated in tissues homeostasis. As such, alterations of its expression or its transcriptional activity have been studied and linked to a spectrum of diseases in organs and tissues of different origins. Indeed, an altered COUP-TFII expression and activity may cause infertility, abnormality in the vascular system and metabolic diseases like diabetes. Moreover, COUP-TFII is actively investigated in cancer research but its role in tumor progression is yet to be fully understood. In this review, we summarize the current understanding of COUP-TFII in healthy and pathological conditions, proposing an updated and critical view of the many functions of this NR.

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miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells

Cited by 24 publications

References 51 publications

CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling

CircDENND2A Promotes Non-small Cell Lung Cancer Progression via Regulating MiR-34a/CCNE1 Signaling

<p>lncRNA KCNQ1OT1 enhances the chemoresistance of oxaliplatin in colon cancer by targeting the miR-34a/ATG4B pathway</p>

COUP-TFII in Health and Disease

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