Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Fang, Wei; Wang, Mofei; Li, Zhen; Wang, Yong; Zhou, Yong

doi:10.3389/fonc.2020.00291

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…Additionally, some miRNAs are associated with resistance to regorafenib in experimental models. In fact, Wei et al showed that long non-coding RNA MIR570MG-sponged miR-145 causes resistance to regorafenib in mouse models of human CRC HCT116R [ 23 ]. The findings of Cai et al demonstrated in vitro that regorafenib treatment is associated with increased expression of miR-34a, highlighting this miRNA as a target for overcoming resistance to this specific treatment [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study

Conde

Earl

Crespo-Toro

et al. 2021

Cancers

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First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment.

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Section: Discussionmentioning

confidence: 99%

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study

Conde

Earl

Crespo-Toro

et al. 2021

Cancers

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show abstract

“…Some lncRNAs were reported to function as oncogenes or tumor suppressors in different types of cancers including CRC (Jin et al, 2020;Shang et al, 2020;Shen et al, 2020;Wang et al, 2020;Wei et al, 2020;Zheng et al, 2020). only few lncRNAs in CRC have been functionally characterized and the biological function of most of the lncRNAs remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Lnc-HSD17B11-1:1 Functions as a Competing Endogenous RNA to Promote Colorectal Cancer Progression by Sponging miR-338-3p to Upregulate MACC1

Zhang

Wang

et al. 2020

Front. Genet.

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Background: Long non-coding RNAs (lncRNAs) play pivotal roles in various kinds of human diseases, especially in cancer. However, regulatory role, clinical significance and underlying mechanisms of lncRNAs in colorectal cancer (CRC) liver metastasis still remain largely unknown. This study aimed to report a novel lncRNA, lnc-HSD17B-11:1, and its functional role in CRC progression. Materials and methods: Differentially expressed lnc-HSD17B11-1:1 was screened and identified from a lncRNA profile microarray. Quantitative real-time PCR was used to determine the expression levels and prognostic values of lncRNA in CRC cohorts. In vitro and in vivo functional experiments were performed to investigate the effects of lnc-HSD17B11-1:1 on tumor growth and metastasis in CRC. Mechanistically, Base Scope, bioinformatics analyses, dual luciferase reporter assay and RNA immunoprecipitation experiments were performed to confirm the association of lnc-HSD17B11-1:1 and miR-338-3p. Dual luciferase reporter assay, qRT-PCR and western blot analysis were performed to assess the relationships among lnc-HSD17B11-1:1, miR-338-3p, and MACC1. Results: Evidently up-regulation of lnc-HSD17B11-1:1 in CRC primary tissues was correlated with the depth of invasion (p = 0.043), clinical stage (p = 0.027), distant metastasis (p = 0.003) and poor prognosis of patients with CRC. lnc-HSD17B11-1:1 promoted CRC cell proliferation, mobility and invasion in vitro and in vivo. Mechanistic analysis revealed that lnc-HSD17B11-1:1 may act as a competing endogenous RNA (ceRNA) by acting as a sponge for miR-338-3p to upregulate the expression of MACC1. Conclusion: These findings suggest that lnc-HSD17B11-1:1 promotes CRC progression through lnc-HSD17B11-1:1/miR-338-3p/MACC1 axis and this might serve as a new diagnostic marker or target for treatment of CRC.

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“…This lncRNA acts as a sponge for miR-145 and inversely regulates the expression of miR-145. At this time, the expression of Smad3, a target of miR-145, increases, thereby promoting resistance to regorafenib [ 96 ]. The BRAF inhibitor vemurafenib is less effective in BRAF -mutated CRC.…”

Section: Molecular Targeted Therapeutic Drugs and Resistancementioning

confidence: 99%

MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

et al. 2021

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Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment.

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Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling

Cited by 5 publications

References 28 publications

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study

Lnc-HSD17B11-1:1 Functions as a Competing Endogenous RNA to Promote Colorectal Cancer Progression by Sponging miR-338-3p to Upregulate MACC1

MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

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