Molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity

Zhu, Jiamin; Chen, Shusen; Yang, Baixia; Mao, Weidong; Yang, Xi; Cai, Jing

doi:10.1042/bsr20190590

Cited by 38 publications

(26 citation statements)

References 77 publications

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“…[ 9 ] In recent years, series of radioresistance‐associated lncRNAs (e.g., HOTAIR, BOKAS, and lncRNA‐p21) have been reported and regulating their expression can induce multiple biological changes, such as blockage of DNA damage repair and promotion of apoptosis. [ 12,35 ] Genome‐wide analysis has shown that a large fraction of the human genome (≈98%) cannot encode proteins but can be transcribed into “non‐coding RNAs” that may exert their biological functions. [ 13 ] Therefore, the number of currently identified radioresistance‐associated lncRNAs is still very low and much more efforts need to be made to discover new functional lncRNAs and elucidate their regulatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, series of functional lncRNAs have been identified as key factors to induce radioresistance by regulating the expression of target genes at transcriptional or post‐transcriptional levels. [ 11,12 ] Although the regulatory mechanisms of these lncRNAs have been extensively elucidated, their clinical translation is significantly hindered because few efforts have been focused on developing effective in vivo delivery strategies to regulate the biological functions of lncRNAs. In addition, compared to the billions of intracellular lncRNAs that may exert their biological functions, [ 13 ] the proportion of currently discovered radioresistance‐associated lncRNAs is still very low and thus more functional lncRNAs and their regulatory mechanisms need to be explored.…”

Section: Introductionmentioning

confidence: 99%

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Nanoparticles (NPs)‐Meditated LncRNA AFAP1‐AS1 Silencing to Block Wnt/β‐Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy

Dinglin

et al. 2020

Advanced Science

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Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament‐associated protein 1 antisense RNA1 (lncAFAP1‐AS1) is identified as a key factor in inducing radioresistance of triple‐negative breast cancer (TNBC) via activating the Wnt/β‐catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction‐responsive nanoparticle (NP) platform is engineered for effective lncAFAP1‐AS1 siRNA (siAFAP1‐AS1) delivery. Systemic delivery of siAFAP1‐AS1 with the reduction‐responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1‐AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1‐AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1‐AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoparticles (NPs)‐Meditated LncRNA AFAP1‐AS1 Silencing to Block Wnt/β‐Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy

Dinglin

et al. 2020

Advanced Science

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“…Numerous studies have confirmed that lncRNAs regulate the radiosensitivity of cancer cells, including HCC cells. 9 For instance, NEAT1_2 depletion enhanced HCC cell radiosensitivity by modulating miR-101-3p and repressing WEE1. 24 Additionally, lncRNA H19 triggered the radioresistance of HCC cells by acting as a ceRNA for miR-193a-3p and upregulating PSEN1.…”

Section: Discussionmentioning

confidence: 99%

“…8 Besides, more and more investigations have manifested that lncRNAs exert a vital effect on the radiosensitivity of tumor cells by functioning as competing endogenous RNA (ceRNA). 9 For example, PTPRG-AS1 facilitates radioresistance in nasopharyngeal carcinoma by sponging microRNA-194-3p and increasing PRC1 expression. 10 Besides, LINC00483 silencing potentiates radiosensitivity in lung adenocarcinoma by regulating the microRNA-144/ HOXA10 axis.…”

Section: Introductionmentioning

confidence: 99%

<p>Knockdown of LINC00473 Enhances Radiosensitivity in Hepatocellular Carcinoma via Regulating the miR-345-5p/FOXP1 Axis</p>

Zhang¹,

Huang²,

Chen³

et al. 2020

OTT

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Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Radioresistance is a significant obstacle in HCC therapy. Long non-coding RNA 473 (LINC00473) has been found to impair the effect of radiotherapy. This study aimed to explore the function and molecular basis of LINC00473 in the radiosensitivity of HCC cells. Methods: The levels of LINC00473, miR-345-5p and Forkhead Box P1 (FOXP1) were determined by quantitative real-time polymerase chain reaction. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Survival fraction was calculated by colony survival assay after exposure to different doses of radiation. Cell apoptosis was evaluated by flow cytometry. The interaction among LINC00473, miR-345-5p and FOXP1 was confirmed by dual-luciferase reporter assay. The protein level of FOXP1 was detected by Western blot assay. Results: LINC00473 and FOXP1 were up-regulated, while miR-345-5p was down-regulated in HCC tissues and cells. Radiation elevated LINC00473 expression in a dose-and time-dependent manner. Depletion of LINC00473 inhibited proliferation and heightened radiosensitivity and apoptosis in HCC cells. In addition, LINC00473 was a sponge of miR-345-5p. Also, miR-345-5p overexpression sensitized HCC cells to radiation. Moreover, miR-345-5p directly targeted FOXP1. MiR-345-5p inhibition or FOXP1 up-regulation reversed the enhanced radiosensitivity caused by LINC00473 knockdown. Conclusion: LINC00473 contributed to radioresistance in HCC via modulating the miR-345-5p/FOXP1 axis, which might provide a promising diagnostic marker for HCC radiotherapy.

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“…Postoperative radiotherapy is one of the main modalities of GBM treatment, but it often fails to achieve the expected results mainly due to tumor radioresistance. Increasing studies showed that lncRNAs have been found to modulate radiosensitivity by regulating various mechanisms [27].Wang et al reported that lncRNA PVT1 served an oncogenic role and played an important role in radiosensitivity in malignant nasopharyngeal carcinoma via activating the KAT2A acetyltransferase and stabilizing HIF-1α [28]. Another study suggested that lncRNA TP73-AS1 was highly expressed in hepatocellular carcinoma and participated in radioresistance via PTEN/AKT signaling pathway [29].…”

Section: Discussionmentioning

confidence: 99%

LncRNA SBF2-AS1 Promotes Malignant Phenotypes and Radioresistance of Glioblastoma Cells by Impairing miR-338-3p-targeted MAP4K3 Inhibition

Pan¹,

Xu²,

Wang³

et al. 2020

Preprint

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Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumors in adults. LncRNA SBF2-AS1 has been reported to promote malignant progression in multiple human cancers. However, the roles and underlying mechanisms of SBF2-AS1 in GBM are still unknown.Methods: The levels of SBF-AS1 were identified in GBM tissues and normal brain tissues, and in GBM cell lines and normal human astrocytes. The effect of SBF2-AS1 on proliferation, invasion and radiosensitivity was evaluated by CCK-8 assay, transwell assay, γ-H2AX foci assay and clonogenic survival assay in vitro and in vivo. The interactions among SBF2-AS1, miR-338-3p and MAP4K3 were validated through luciferase report, RNA immunoprecipitation and western blot assays. Results: In the present study, we comfirmed that SBF2-AS1 was highly upregulated in GBM tissues and cell lines, and its levels were markedly higher in WHO stage III-IV gliomas compared with WHO stage I-II gliomas. Kaplan-Meier survival analysis revealed that glioma patients with high SBF2-AS1 expression had shorter overall survival than those with low SBF2-AS1 expression. SBF2-AS1 inhibition suppressed the proliferation of GBM cells by down-reguating of Ki-67 and CyclinD1. Moreover, silencing SBF2-AS1 increased the proportion of cells in G1 phase and decreased the proportion of cells in S phase. In addition, SBF2-AS1 inhibition suppressed the invasion of GBM cells by down-reguating of MMP2 and MMP9. Xenograft tumor models revealed that the silencing of SBF2-AS1 inhibited tumor growth in vivo. Moreover, the silencing of SBF2-AS1 significantly sensitized GBM cells to radiation in vitro and in vivo. Indeed, we observed a persistence of γ-H2AX staining after ionizing radiation, leading to enhanced DNA repair and radioresistance. Mechanistically, SBF2-AS1 inhibition reduced the expression of MAP4K3 by directly binding with miR-338-3p in GBM cells. Conclusions: Our study demonstrated that SBF2-AS1 enhanced cell proliferation, invaison and radioresistance via modulating miR-338-3p/MAP4K3 axis, and it is an attractive therapeutic target to overcome radioresistance of GBM.

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Molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity

Cited by 38 publications

References 77 publications

Nanoparticles (NPs)‐Meditated LncRNA AFAP1‐AS1 Silencing to Block Wnt/β‐Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy

Nanoparticles (NPs)‐Meditated LncRNA AFAP1‐AS1 Silencing to Block Wnt/β‐Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy

<p>Knockdown of LINC00473 Enhances Radiosensitivity in Hepatocellular Carcinoma via Regulating the miR-345-5p/FOXP1 Axis</p>

LncRNA SBF2-AS1 Promotes Malignant Phenotypes and Radioresistance of Glioblastoma Cells by Impairing miR-338-3p-targeted MAP4K3 Inhibition

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