CircVRK1 regulates tumor progression and radioresistance in esophageal squamous cell carcinoma by regulating miR-624-3p/PTEN/PI3K/AKT signaling pathway

He, Yunlong; E, Mingyan; Wang, Chunbo; Liu, Guohui; Shi, Manru; Liu, Shuang

doi:10.1016/j.ijbiomac.2018.11.273

Cited by 67 publications

(55 citation statements)

References 30 publications

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“…PTEN mRNA is the competing target of many miRNAs, e.g. miR-624-3p, miR-130a, and miR-21 (40)(41)(42). There are several potential binding sites of miR-21 on the PTEN 3'UTR, such as GAUAAG and UCUG*UG*GCUA (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…PTEN is an inhibitor of the PI3K/Akt signaling pathway (45), and the PTEN/Akt axis is a pivotal regulatory pathway in IR-induced cell apoptosis. He et al demonstrated that overexpression of circVRK1 could reverse the radioresistance of esophageal squamous carcinoma cells by regulating the miR-624-3p/PTEN/PI3K/Akt signaling pathway (40). Wang et al reported that miR-29a regulated the radiosensitivity of human intestinal cells by activating the PTEN/PI3K/Akt signaling pathway (46).…”

Section: Discussionmentioning

confidence: 99%

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Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

et al. 2020

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Radioresistance hinders the therapeutic outcomes of radiotherapy in non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been demonstrated to participate in the regulation of multiple cell behaviors, whether they can modulate the radiosensitivity of NSCLC and the underlying molecular mechanisms have not been well investigated. In the present study, it was revealed that NSCLC NCI-H460 cells were more sensitive to ionizing radiation (IR) than A549 cells. Using the RNA-Seq method, four highly differentially expressed lncRNAs were identified, including the growth arrest-specific transcript 5 (GAS5), syntaxin binding protein 5 antisense RNA 1 (STXBP5-AS1), metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and X-inactive specific transcript (XIST), which were predicted to play roles in the acquisition of radiosensitivity. Using real-time quantitative PCR (qPCR), it was demonstrated that lncRNA GAS5 was significantly upregulated in NCI-H460 cells but not in A549 cells during IR. Mechanistically, it was demonstrated that overexpression of lncRNA GAS5 decreased the level of microRNA-21 (miR-21). Overexpression of lncRNA GAS5 or suppression of miR-21 markedly increased the IR-induced cell apoptosis of A549 cells. It was also demonstrated that overexpression of lncRNA GAS5 increased PTEN expression and suppressed Akt phosphorylation through the modulation of miR-21. Notably, it was revealed that IR enhanced the interaction between lncRNA GAS5 and the miR-21/PTEN/Akt axis. In summary, the present findings revealed that lncRNA GAS5 has a radiosensitization effect on NSCLC, indicating the potential application of lncRNA GAS5 in NSCLC radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

et al. 2020

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“…Recently, circRNAs are also proved to be associated with cancer radioresistance. In EC, for example, circVRK1 is found to be downregulated while overexpression of it can inhibit cell proliferation, migration, and EMT, resulting in reversed radioresistance by miR-624-3p/ PTEN/PI3K/Akt signaling pathway [206]. In GBM, circ-AKT3 is reported to encode AKT3-174aa, a novel tumor suppressor protein, and enhance radiation sensitivity cells by negatively regulating the PI3K/Akt pathway [207].…”

Section: Circrnas In Cancer Radioresistancementioning

confidence: 99%

Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

et al. 2020

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As the standard treatments for cancer, chemotherapy and radiotherapy have been widely applied to clinical practice worldwide. However, the resistance to cancer therapies is a major challenge in clinics and scientific research, resulting in tumor recurrence and metastasis. The mechanisms of therapy resistance are complicated and result from multiple factors. Among them, non-coding RNAs (ncRNAs), along with their modifiers, have been investigated to play key roles in regulating tumor development and mediating therapy resistance within various cancers, such as hepatocellular carcinoma, breast cancer, lung cancer, gastric cancer, etc. In this review, we attempt to elucidate the mechanisms underlying ncRNA/modifier-modulated resistance to chemotherapy and radiotherapy, providing some therapeutic potential points for future cancer treatment.

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“…CircVRK1 is decreased in ESCC tissues, and patients with low level of circVRK1 have a poor prognosis. This is probably because circVRK1, as a sponge of miR-624-3p, decreases the PTEN/PI3K-mediated activity of AKT and inhibits EMT, which enhances the sensitivity of ESCC cells to radiotherapy [104].…”

Section: Esophageal Cancermentioning

confidence: 99%

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

et al. 2020

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Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products of pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions of diverse molecules, including non-coding RNAs, mRNAs, DNAs and proteins, to regulate cell activities in physiology and pathology. Accumulating evidence indicates that circRNAs play critical roles in tumor genesis, development, and sensitivity to radiation and chemotherapy. Radiotherapy and chemotherapy are two primary types of intervention for most cancers, but their therapeutic efficacies are usually retarded by intrinsic and acquired resistance. Thus, it is urgent to develop new strategies to improve therapeutic responses. To achieve this, clarification of the underlying mechanisms affecting therapeutic responses in cancer is needed. This review summarizes recent progress and mechanisms of circRNAs in cancer resistance to radiation and chemotherapy, and it discusses the limitations of available knowledge and potential future directions.

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CircVRK1 regulates tumor progression and radioresistance in esophageal squamous cell carcinoma by regulating miR-624-3p/PTEN/PI3K/AKT signaling pathway

Cited by 67 publications

References 30 publications

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

Long non‑coding RNA GAS5 increases the radiosensitivity of A549 cells through interaction with the miR‑21/PTEN/Akt axis

Role of non-coding RNAs and RNA modifiers in cancer therapy resistance

Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

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