Identification of differentially expressed circulating serum microRNA for the diagnosis and prognosis of Indian non–small cell lung cancer patients

Kumar, Sachin; Sharawat, Surender Kumar; Ali, Ashraf; Gaur, Vikas; Malik, Prabhat Singh; Kumar, Sunil; Mohan, Anant; Guleria, Randeep

doi:10.1016/j.currproblcancer.2020.100540

Cited by 47 publications

(35 citation statements)

References 74 publications

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“…Firstly, our data revealed the poor expression of miR-320a in NSCLC cells and tissue samples, which promoted radiosensitivity of NSCLC by reducing NSCLC cell proliferation and enhancing apoptosis. Consistent with our study, Kumar et al (2020) demonstrated that miR-320a was downregulated in the serum of NSCLC patients. Additionally, the poor expression of miR-320 has also been demonstrated in NSCLC tissues and cells (Wang et al, 2017).…”

Section: Discussionsupporting

confidence: 92%

Overcoming of Radioresistance in Non-small Cell Lung Cancer by microRNA-320a Through HIF1α-Suppression Mediated Methylation of PTEN

Yuan

et al. 2020

Front. Cell Dev. Biol.

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Background Radioresistance is a major challenge in the use of radiotherapy for the treatment of lung cancer while microRNAs (miRs) have been reported to participate in multiple essential cellular processes including radiosensitization. This study was conducted with the main objective of investigating the potential role of miR-320a in radioresistance of non-small cell lung cancer (NSCLC) via the possible mechanism related to HIF1α, KDM5B, and PTEN. Methods Firstly, NSCLC radiosensitivity-related microarray dataset GSE112374 was obtained. Then, the expression of miR-320a, HIF1α, KDM5B, and PTEN was detected in the collected clinical NSCLC samples, followed by Pearson’s correlation analysis. Subsequently, ChIP assay was conducted to determine the content of the PTEN promoter fragment enriched by the IgG antibody and H3K4me3 antibody. Finally, a series of in vitro and in vivo assays were performed in order to evaluate the effects of miR-320a on radioresistance of NSCLC with the involvement of HIF1α, KDM5B, and PTEN. Results The microarray dataset GSE112374 presented with a high expression of miR-320a in NSCLC radiosensitivity samples, which was further confirmed in our clinical samples with the use of reverse transcription-quantitative polymerase chain reaction. Moreover, miR-320a negatively targeted HIF1α, inhibiting radioresistance of NSCLC. Interestingly, miR-320a suppressed the expression of KDM5B, and KDM5B was found to enhance the radioresistance of NSCLC through the downregulation of PTEN expression. The inhibition of miR-320a in radioresistance of NSCLC was also reproduced by in vivo assay. Conclusion Taken together, our findings were suggestive of the inhibitory effect of miR-320a on radioresistance of NSCLC through HIF1α-suppression mediated methylation of PTEN.

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Section: Discussionsupporting

confidence: 92%

Overcoming of Radioresistance in Non-small Cell Lung Cancer by microRNA-320a Through HIF1α-Suppression Mediated Methylation of PTEN

Yuan

et al. 2020

Front. Cell Dev. Biol.

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“…We observed that the expression of multiple miRs was significantly increased or attenuated. Similar observations have been previously reported using serum from patients with other cancer types ( 29 , 30 ). Here, we focused on miR-1246, a miR with increased expression, and miR-106b, a miR with attenuated expression.…”

Section: Discussionsupporting

confidence: 91%

Usefulness of serum miR‑1246/miR‑106b ratio in patients with esophageal squamous cell carcinoma

et al. 2020

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The function of microRNAs (miRs) is associated with the development and progression of various malignancies, with miRs presenting stably in the serum. The current study assessed the role of miR-1246 and miR-106b in the serum of patients with esophageal squamous cell carcinoma (ESCC). A comprehensive microarray analysis of miR expression was performed using the serum of patients with ESCC, which were subsequently validated via reverse transcription-quantitative PCR. A total of 55 test samples were obtained from Chiba University and 101 validation samples were gained from Chiba Cancer Center. The results revealed that miR-1246 expression significantly increased and miR-106b expression significantly decreased in each cohort. Receiver operating characteristic analysis revealed that the area under the curve (AUC) value of miR-1246 was 0.816 (sensitivity, 72.7%; specificity, 69.2%) and 0.779 (sensitivity, 71.3%; specificity, 70.6%) for the test and validation cohorts, respectively. The AUC of miR-106b was 0.716 (sensitivity, 65.5%; specificity, 61.6%) and 0.815 (sensitivity, 74.3%; specificity, 73.5%), respectively. In addition, the AUC of the miR-1246/miR-106b ratio was 0.901 (sensitivity, 80.0%; specificity, 80.0%) and 0.903 (sensitivity, 82.1%; specificity, 82.3%), respectively, which indicated a higher diagnostic ability compared with that of miR-1246 or miR-106b alone. The high miR-1246/miR-106b ratio group was associated with clinicopathological factors such as depth of invasion, progression, lymph node metastasis, and poor prognosis. Therefore, effective biomarkers may be generated by combining individual miRs obtained by comprehensive analysis of ESCC patient sera.

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“…Through bioinformatics analysis, dual-luciferase reporter assay, RIP and RNA pull-down assay, miR-375 was validated as a target of circ_0086720. MiR-375 was reported to be downregulated in NSCLC [32]. Consistently, our study also proved that miR-375 expression was lessened in NSCLC tissues and decreased more in radioresistant NSCLC tissues.…”

Section: Discussionsupporting

confidence: 87%

Circ_0086720 knockdown strengthens the radiosensitivity of non-small cell lung cancer via mediating the miR-375/SPIN1 axis

Jin

Sheng

et al. 2021

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Radioresistance is an important cause of cancer treatment failure. Circular RNAs (circRNAs) play crucial roles in cancer development, including the radioresistance. This research aimed to determine the function and related mechanism of circ_0086720 in the radioresistance of non-small cell lung cancer (NSCLC). The expression of circ_0086720, miR-375, and Spindlin 1 (SPIN1) was measured using a quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival fraction was analyzed using colony formation assay, and cell apoptosis was monitored b y flow cytometry assay. The activities of caspase3 and caspase9 were assessed using the corresponding commercial kits. The ed by western blot. Bioinformatics analysis was performed to predict the targets of circ_0086720 and miR-375. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were conducted to validate the interaction between miR-375 and circ_0086720 or SPIN1. The animal model was constructed to ascertain the role of circ_0086720 in vivo. The expression of circ_0086720 and SPIN1 was increased in the radioresistant NSCLC tissues, while miR-375 expression was decreased. The circ_0086720 knockdown sensitized NSCLC cells to the radiation to further inhibit cell survival and induce cell apoptosis. Circ_0086720 targeted miR-375 and suppressed miR-375 expression, and miR-375 bound to SPIN1 to impair SPIN1 expression. miR-375 deficiency or SPIN1 overexpression could attenuate circ_0086720 knockdown-mediated radiosensitivity. The circ_0086720 knockdown also enhanced radiosensitivity to further block tumor growth in vivo. To conclude, circ_0086720 downregulation enhanced the sensitivity of NSCLC to radiation by regulating the miR-375/SPIN1 axis, contributing to the improvement of the radiotherapies in NSCLC.

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Identification of differentially expressed circulating serum microRNA for the diagnosis and prognosis of Indian non–small cell lung cancer patients

Cited by 47 publications

References 74 publications

Overcoming of Radioresistance in Non-small Cell Lung Cancer by microRNA-320a Through HIF1α-Suppression Mediated Methylation of PTEN

Overcoming of Radioresistance in Non-small Cell Lung Cancer by microRNA-320a Through HIF1α-Suppression Mediated Methylation of PTEN

Usefulness of serum miR‑1246/miR‑106b ratio in patients with esophageal squamous cell carcinoma

Circ_0086720 knockdown strengthens the radiosensitivity of non-small cell lung cancer via mediating the miR-375/SPIN1 axis

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