H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway

Wu, Kefeng; Liang, Weicheng; Lu, Feng; Pang, Jianxin; Waye, Mary Miu Yee; Zhang, Jinfang; Fu, Weiming

doi:10.1016/j.yexcr.2016.12.003

Cited by 91 publications

(68 citation statements)

References 28 publications

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“…Overexpression of maternally expressed gene 3 (MEG3), a prognostic factor for CRC, promoted chemosensitivity by enhancing oxaliplatin-induced cell apoptosis [24]. H19 conferred methotrexate resistance through activating Wnt/β-catenin pathway [25]. Increasing studies revealed the oncogenic function of XIST in several tumors, such as gastric cancer [26], nasopharyngeal carcinoma [27], and hepatocellular carcinoma [28], through inducing cell proliferation, invasion and metastasis..…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. Methods: The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. Results: XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. Conclusion: XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.

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Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Zhu

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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“…Additionally, the Wnt/β-catenin signaling pathway plays a major role in promoting the progression of malignant tumors, indicating that it regulates cell cycle and apoptosis [ 20 ]. The Wnt/β-catenin signaling activates HT-29-R cells, and H19 knockdown arrests the signaling in the parental cells [ 21 ]. Moreover, c-Myc and cyclin D1 are considered as genes of the Wnt/β-catenin signaling pathway, and knockdown of CUL4B promotes the cyclin D1- and c-Myc-regulated apoptosis in colorectal cancer cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA H19 induces hippocampal neuronal apoptosis via Wnt signaling in a streptozotocin-induced rat model of diabetes mellitus

Zhao

Luo

et al. 2017

Oncotarget

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Defects in hippocampal synaptic plasticity and disorders of memory and learning are the central nervous system complications of diabetes mellitus (DM). Here, we used a streptozotocin-induced rat DM model to investigate the effects of long non-coding RNA H19 (lncRNA H19) on learning and memory and apoptosis of hippocampal neurons, and the involvement of the Wnt signaling. Our data demonstrate that lncRNA H19 is highly expressed in rats with DM. Over-expression of lncRNA H19 increased positioning navigation latency in DM rats and decreased duration of space exploration. lncRNA H19 over-expression also increased hippocampal neuronal apoptosis and expression of Wnt3, β-catenin, TCF-1, Bax, caspase-8 and caspase-3. By contrast, expression of GSK-3β and Bcl-2 was suppressed in DM rats over-expressing lncRNA H19. These results suggest that lncRNA H19 induces hippocampal neuronal apoptosis via Wnt signaling, and that inhibition of lncRNA H19 may serve as a promising novel target for the treatment of cognitive decline in patients with DM.

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“…Its high expression level indicates poor overall survival and free of progression [66] Cisplatin/gemcitabine Modulating miR-196a-5p of bladder carcinoma cells NCRAN [67] Cisplatin Upregulating drug resistance; suppressing apoptosis LET/NF90/miR-145 [68] Gemcitabine Upregulating TGFβ1 GAS5 [69] Doxorubicin Promoting apoptosis; depressing the expression of anti-apoptosis protein Bcl-2 Lung cancer HOTAIR Crizotinib [70] Activating autophagy by inhibiting the phosphorylation of ULK1 Gefitinib [71] Activating Bax/Caspase-3 and TGF-α/EGFR signaling AK126698 [72] Cisplatin Suppressing canonical Wnt signaling pathway; downregulating cisplatin resistance MEG3 [41] Cisplatin Enhancing cisplatin sensitivity via regulating miR-21-5p/SOX7 axis; activating p53 and Bcl-xl of LAD cells XIST [32] Cisplatin Enhancing the drug resistance of NSCLC cells via suppressing autophagy AK001796 [73] Cisplatin Upregulating the expression of ANRIL KCNQ1OT1 [74] Paclitaxel Upregulating the chemoresistance MIAT [9] Gefitinib Regulating miR-34a TUG1 [75] Cisplatin Regulating LIMK2b via EZH2 ANRIL [76] Cisplatin Inhibits proliferation, induces apoptosis Colorectal cancer H19 [77] Doxorubicin Overexpression of H19 activating Wnt/β-catenin pathway CUDR [78] 5-fluorouracil Upregulating miR-195 Oxaliplatin…”

Section: Mutations Of Drug Targetsmentioning

confidence: 99%

Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance

Zhao¹,

Shan²,

He³

et al. 2019

J. Cancer

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Drug resistance is an important cause of failure in cancer chemotherapies. A large number of long noncoding RNAs (lncRNAs) have been found to be related to drug resistance in cancers. Therefore, lncRNAs provide potential targets for cancer therapies. The lncRNAs involved in cancer drug resistance are attracting interest from an increasing number of researchers. This review summarizes the latest research on the mechanisms and functions of lncRNAs in cancer drug resistance and envisages their future developments and therapeutic applications. This research suggests that lncRNAs regulate drug resistance through multiple mechanisms. LncRNAs do not affect drug resistance directly; usually, they do so by regulating the expression of some intermediate regulatory factors. In addition, lncRNAs exhibit a diversity of functions in cancer drug resistance. The overexpression of most lncRNAs promotes drug resistance, while a few lncRNAs have inhibitory effects.

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H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway

Cited by 91 publications

References 28 publications

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

Long non-coding RNA H19 induces hippocampal neuronal apoptosis via Wnt signaling in a streptozotocin-induced rat model of diabetes mellitus

Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance

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