Radiotherapy resistance: identifying universal biomarkers for various human cancers

Larionova, Irina; Rakina, Militsa; Ivanyuk, E. E.; Trushchuk, Yulia; Чернышова, А. Л.; Denisov, Evgeny V.

doi:10.1007/s00432-022-03923-4

Cited by 29 publications

(13 citation statements)

References 190 publications

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“…[ 38 ] Although radiotherapy is considered a primary treatment for various solid cancers, including EC, it still faces a significant challenge: tumor cell radioresistance. [ 39 ] The hypoxic microenvironment plays a crucial role in contributing to radioresistance by interfering with the fixation of DNA damage, primarily driven by the activation of HIF‐1α, a transcription factor that is constitutively expressed under hypoxic conditions and involved in cell cycle deregulation, proliferation, and apoptosis. [ 40 ] Notably, emerging evidence has highlighted the involvement of lncRNAs in the hypoxic response and their complex interaction with HIF‐1α.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia‐induced factor‐1α promotes radioresistance of esophageal cancer cells by transcriptionally activating LINC01116 and suppressing miR‐3612 under hypoxia

Zhang,

Wang,

et al. 2023

J Biochem & Molecular Tox

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Esophageal cancer (EC) is a challenging tumor to treat with radiotherapy, often exhibiting resistance to this treatment modality. To explore the factors influencing radioresistance, we focused on the role of hypoxia‐induced factor‐1α (HIF‐1α), and its interaction with the long noncoding RNA long intergenic nonprotein coding RNA 1116 (LINC01116). We analyzed the LINC01116 expression in EC and EC cell lines/human normal esophageal epithelial cell line (Het‐1A). LINC01116 was silenced/overexpressed in EC109/KYSE30 cells under hypoxia, followed by radioresistance assessment. We measured HIF‐1α levels in hypoxic EC cells and further validated the binding of HIF‐1α with LINC01116, analyzing their interaction in EC cells. We then performed experiments in EC109 cells by transfection them with sh‐HIF‐1α/oe‐LINC01116 to verify the effects. Additonally, we analyzed the localization of LINC01116 and its binding with miR‐3612, followed by a combined experiment performed to validate the results. Our findings indicated that LINC01116 was highly expressed in EC and further elevated in hypoxic EC cells. LINC01116 was expressed at a high level in EC, which was further elevated in EC cells under hypoxic conditions. Knockdown of LINC01116 triggered EC cell apoptosis, thus suppressing radioresistance. Further investigation revealed that HIF‐1α transcriptionally activated LINC01116 expression under hypoxia, and silencing HIF‐1α lowered EC cell radioresistance by downregulating LINC01116. Under hypoxic conditions, LINC01116 could function as a sponge for miR‐3612 and inhibit its expression. This interaction between LINC01116 and miR‐3612 played a crucial role in mediating radioresistance in EC cells. Briefly, under hypoxic conditions, HIF‐1α facilitates radioresistance of EC cells by transcriptionally activating LINC01116 expression and downregulating miR‐3612.

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Section: Discussionmentioning

confidence: 99%

Hypoxia‐induced factor‐1α promotes radioresistance of esophageal cancer cells by transcriptionally activating LINC01116 and suppressing miR‐3612 under hypoxia

Zhang,

Wang,

et al. 2023

J Biochem & Molecular Tox

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“…Drug-therapy or radiotherapy resistance was a critical factor for tumor treatment failure and the development of locoregional relapse and distant metastases which seriously affected the prognosis of tumor patients. Different from the primary drug or radiotherapy resistance caused by genetic change, this acquired resistance were often induced by regularly exposing tumor cells to conventional drug-therapy or radiotherapy [167,168]. It followed that the prediction and overcoming of drug-therapy or radiotherapy resistance were particularly important.…”

Section: Tumor-driven Exosomal Circrnas and Diagnosismentioning

confidence: 99%

Regulatory mechanisms and clinical applications of tumor-driven exosomal circRNAs in cancers

Meng¹,

Dong²,

Bao³

et al. 2023

Int. J. Med. Sci.

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Malignant tumors seriously affect people's survival and prognosis. Exosomes, as vesicle structures widely existing in human tissues and body fluids, are involved in cell-to-cell transmission. Tumor-derived exosomes were secreted from tumors and involved in the development of carcinogenesis. Circular RNA (circRNA), a novel member of endogenous noncoding RNAs, is widespread in human and play a vital role in many physiological or pathological processes. Tumor-driven exosomal circRNAs are often involved in tumorigenesis and development including the proliferation, invasion, migration and chemo-orradiotherapy sensitivity of tumor cell by multiple regulatory mechanisms. In this review, we will elaborate the roles and functions of tumor-driven exosomal circRNAs in cancers which may be used as potential cancer biomarkers and novel therapeutic targets.

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“…Amounts of evidence demonstrated that the preferential activation of DNA damage repair, cell cycle checkpoint, and epithelial–mesenchymal transition (EMT) development are typically associated with radiation‐induced resistance. 5 , 6 Inhibition of DNA damage repair pathways could enhance the radiosensitivity of cancer cells. A large amount of DNA damage repair–related molecules were developed to be clinical therapy targets, such as p53 and cell cycle checkpoint proteins.…”

Section: Introductionmentioning

confidence: 99%

TXNL4B regulates radioresistance by controlling the PRP3‐mediated alternative splicing of FANCI

Zhao

Jing

Xiao

et al. 2023

MedComm

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Ionizing radiation (IR) has been extensively used for cancer therapy, but the radioresistance hinders and undermines the radiotherapy efficacy in clinics greatly. Here, we reported that the spliceosomal protein thioredoxin‐like 4B (TXNL4B) is highly expressed in lung tissues from lung cancer patients with radiotherapy. Lung cancer cells with TXNL4B knockdown illustrate increased sensitivity to IR. Mechanistically, TXNL4B interacts with RNA processing factor 3 (PRP3) and co‐localizes in the nucleus post‐IR. Nuclear localization of PRP3 promotes the alternative splicing of the Fanconi anemia group I protein (FANCI) transcript variants, FANCI‐12 and FANCI‐13. PRP3 regulates alternative splicing of FANCI toward the two variants, FANCI‐12 and FANCI‐13. Radioresistance was greatly enhanced through the combination of PRP31 and PRP8, the critical components of core spliceosome promoted by PRP3. Notably, the inhibition of PRP3 to suppress the production of FANCI‐12 would deprive PRP31 and PRP8 of such interaction. As a result, cell cycle G2/M arrest was induced, DNA damage repair was delayed, and radiosensitivity was improved. Collectively, our study highlights potential novel underlying mechanisms of the involvement of TXNL4B and alternative splicing in radioresistance. The results would benefit potential cancer radiotherapy.

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Radiotherapy resistance: identifying universal biomarkers for various human cancers

Cited by 29 publications

References 190 publications

Hypoxia‐induced factor‐1α promotes radioresistance of esophageal cancer cells by transcriptionally activating LINC01116 and suppressing miR‐3612 under hypoxia

Hypoxia‐induced factor‐1α promotes radioresistance of esophageal cancer cells by transcriptionally activating LINC01116 and suppressing miR‐3612 under hypoxia

Regulatory mechanisms and clinical applications of tumor-driven exosomal circRNAs in cancers

TXNL4B regulates radioresistance by controlling the PRP3‐mediated alternative splicing of FANCI

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