Functional Peptides Encoded by Long Non-Coding RNAs in Gastrointestinal Cancer

Chen, Yao; Long, Weili; Zhao, Yueshui; Wu, Xu; Li, Mingxing; Du, Fukuan; Chen, Yu; Yang, Zijian; Wen, Qinglian; Yi, Tao; Xiao, Zhangang; Shen, Jing

doi:10.3389/fonc.2021.777374

Cited by 14 publications

(10 citation statements)

References 117 publications

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“…The wealth of literature on lncRNAs in cancer has taught us that their functions involve regulation of miRNAs ( 15 , 16 ). Therefore, our next task was to find a miRNA that is relevant to TMZ resistance in our glioma models.…”

Section: Resultsmentioning

confidence: 99%

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Xia

et al. 2022

Front. Oncol.

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The advanced grade glioblastomas are characterized by dismal five-year survival rates and are associated with worse outcomes. Additionally, resistance to therapies is an additional burden responsible for glioma associated mortality. We studied the resistance against temozolomide (TMZ) as a surrogate to understand the mechanism of therapy resistance in glioma cancer cells. Screening of three glioma cells lines, A172, LN229 and SF268 revealed that SF268 glioma cells were particularly resistant to TMZ with the IC-50 of this cell line for TMZ ten times higher than for the other two cell lines. A role of lncRNAs in glioma progression has been identified in recent years and, therefore, we focused on lncRNAs for their role in regulating TMZ resistance in glioma cancer cells. lncRNA HOTTIP was found to be particularly elevated in SF268 cells and over-expression of HOTTIP in both A172 and LN229 remarkably increased their TMZ IC-50s, along with increased cell proliferation, migration, clonogenicity and markers of angiogenesis and metastasis. As a mechanism we observed increased expression of miRNA-10b and mesenchymal markers Zeb1/Zeb2 and reduced expression of E-cadherin in SF268 cells indicating a role of EMT in TMZ resistance. A172 and LN229 cells with overexpressed HOTTIP also had similarly induced EMT and the elevated miR-10b levels. Further, silencing of miR-10b in HOTTIP overexpressing cells as well as the SF268 cells reversed EMT with associated sensitization of all the tested cells to TMZ. Our results thus present a case for HOTTIP in native as well as acquired resistance of glioma cells against chemotherapy, with a key mechanistic role of EMT and the miR-10b. Thus, HOTTIP as well as miR-10b are critical targets for glioma therapy, and need to be tested further.

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Section: Resultsmentioning

confidence: 99%

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Xia

et al. 2022

Front. Oncol.

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“…In the past few years, several studies have highlighted association of previously unsuspected RNAs to ribosomes in the context of cancer, with wide-ranging consequences on cancer biology ( 84–87 ). For example, non-canonical association of non-coding RNAs (ncRNAs) with ribosomes has been shown to result in the production of functional peptides in multiple cancers, controlling tumor initiation or growth ( 88–94 ). Moreover, polysome profiling datasets enable us to easily investigate such unconventional RNA associations to ribosomes.…”

Section: Resultsmentioning

confidence: 99%

Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation

et al. 2022

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Emerging evidence associates translation factors and regulators to tumorigenesis. However, our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and poly(ribo)some profiling, we investigated global translation changes that occur during acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit an overall decrease in mRNA translation with a specific deregulation in the abundance of proteins involved in mitochondrial processes and in translational regulation. However, several mRNAs escape this translational downregulation and are nonetheless bound to heavy polysomes in enzalutamide-resistant cells suggesting active translation. Moreover, expressing these corresponding genes in enzalutamide-sensitive cells promotes resistance to enzalutamide treatment. We also found increased association of long non-coding RNAs (lncRNAs) with heavy polysomes in enzalutamide-resistant cells, suggesting that some lncRNAs are actively translated during enzalutamide resistance. Consistent with these findings, expressing the predicted coding sequences of known lncRNAs JPX, CRNDE and LINC00467 in enzalutamide-sensitive cells drove resistance to enzalutamide. Taken together, this suggests that aberrant translation of specific mRNAs and lncRNAs is a strong indicator of PCa enzalutamide resistance, which points towards novel therapeutic avenues that may target enzalutamide-resistant PCa.

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“…For instance, lncRNA HOXB-AS3 encodes a conserved 53-amino-acid-long peptide that interacts with hnRNPA1 to repress glucose metabolism reprogramming, thus suppressing colon cancer growth ( 176 ). Notably, the lncRNA peptidome has been established for colorectal adenocarcinoma ( 177 ). Five universally expressed lncRNA peptides show greater expression in tumors than normal tissues, suggesting that they are promising biomarkers for this type of cancer ( 154 ).…”

Section: Ncrnas In Epigenetic Controlmentioning

confidence: 99%

“…Endogenously expressed lncRNAs and circRNAs function as ceRNAs by sequestering miRNAs ( 209 ). This inherent ability of lncRNAs to block the activity of miRNAs was exploited to engineer decoys, also referred to as target mimics or sponges ( 177 ). Both lncRNAs and artificial sponges harbor short sequences that are homologous to miRNA binding sites on their endogenous targets ( 210 ).…”

Section: Ncrnas In Epigenetic Controlmentioning

confidence: 99%

Modulating epigenetic modifications for cancer therapy (Review)

et al. 2023

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Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non-coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA-based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer. Contents1. Introduction 2. Epigenetic mechanisms in cancer, roles in carcinogenesis and therapeutic approaches 3. ncRNAs in epigenetic control 4. Conclusions

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Functional Peptides Encoded by Long Non-Coding RNAs in Gastrointestinal Cancer

Cited by 14 publications

References 117 publications

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

HOTTIP Mediated Therapy Resistance in Glioma Cells Involves Regulation of EMT-Related miR-10b

Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation

Modulating epigenetic modifications for cancer therapy (Review)

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