circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

[Erratum] circRNA_001275 upregulates Wnt7a expression by competitively sponging miR­370­3p to promote cisplatin resistance in esophageal cancer.

Following the publication of the above article, the authors have realized that certain intended corrections were not carried over to the published version of the article. First, the description of the results of Figs. 5 and 6 did not match the figures; Edu and Transwell invasion assays were intended to have been excluded from the manuscript during the proofreading stage, although these data were presented in the description of the results for Figs. 5 and 6. Consequently, the text for the "circRNA_001275 promotes cell proliferation" subsection of the Results section towards the end of p. 153 should have read as follows: "MTT assay was used to detect the effects of circRNA_001275 on cell proliferation. The results showed that cell viability was significantly increased in the circRNA_001275 OE group, and significantly decreased in the si circRNA_001275 group (both P<0.05, Fig. 5A and B), compared with the corresponding control groups." Furthermore, the text in the subsequent subsection ("circRNA_001275 inhibits cell apoptosis") should have read as follows: "Hoechst 33258 staining was used to detect the effects of circRNA_001275 on apoptosis. The apoptosis rate was significantly decreased in the circRNA_001275 OE group, and significantly increased in the si circRNA_001275 group (both P<0.05; Fig. 6), compared with the corresponding control group. Secondly, Fig. 5B was omitted from Fig. 5 in the published article; and thirdly, a higher­resolution version of Fig. 6 was submitted during the revision stages, although the version of this figure that was deemed to have been too low in quality was the one that appeared in the final proofs. The corrected / updated versions of Figs. 5 and 6 are shown opposite. The Editor of International Journal of Oncology regrets that certain of these errors were introduced into the article during the production stages, and apologizes both to the authors and to the readership. [the original article was published in International Journal of Oncology 57: 151­160, 2020; DOI: 10.3892/ijo.2020.5050].

Identification of CircRNA-miRNA-mRNA Regulatory Network in Gastrointestinal Stromal Tumor.

Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA-miRNA-mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA-miRNA-mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with "regulation of biological process," "intracellular organelle," "protein binding," and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA-miRNA-mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.

circRNA_001275 upregulates Wnt7a expression by competitively sponging miR­370­3p to promote cisplatin resistance in esophageal cancer.

Circular RNAs (circRNAs) are aberrantly expressed in various tumors and are associated with tumorigenesis. The present study aimed to determine the role of circRNA_001275 in cisplatin­resistant esophageal cancer. Three pairs of cisplatin­resistant tissues and corresponding adjacent tissues were collected and subjected to circRNA chip analysis. Additionally, the effect of circRNA_001275 on cisplatin­resistant cells was investigated. The relationship between circRNA_001275, microRNAs (miRs) and target genes were analyzed using luciferase assays, and validated via reverse transcription­quantitative PCR (RT­qPCR) and western blotting. The results showed that circRNA_001275 was significantly upregulated in cisplatin­resistant esophageal cancer tissues and cells (P<0.05). Overexpression of circRNA_001275 promoted the proliferation and invasion, and decreased the apoptosis of cisplatin­resistant cells. On the other hand, circRNA_001275 silencing inhibited cell proliferation and invasion, and promoted cell apoptosis (P<0.05). Dual­luciferase reporter assays revealed that circRNA_001275 directly binds to miR­370­3p, and that Wnt family member 7A (Wnt7a) is targeted by miR­370­3p. RT­qPCR and western blotting further demonstrated that circRNA_001275 serves as an miR­370­3p sponge to upregulate Wnt7a expression. In conclusion, the present study revealed that circRNA_001275 was upregulated in cisplatin­resistant esophageal cancer and promoted cisplatin resistance by sponging miR­370­3p to upregulate Wnt7a expression. Therefore, circRNA_001275 may serve as a potential diagnostic biomarker and therapeutic target for patients with cisplatin­resistant esophageal cancer.

Concordance Study Between IBM Watson for Oncology and Real Clinical Practice for Cervical Cancer Patients in China: A Retrospective Analysis.

Watson for Oncology (WFO) is a artificial intelligence clinical decision-support system with evidence-based treatment options for oncologists. WFO has been gradually used in China, but limited reports on whether WFO is suitable for Chinese patients. This study aims to investigate the concordance of treatment options between WFO and real clinical practice for Cervical cancer patients retrospectively. We retrospectively enrolled 300 cases of cervical cancer patients. WFO provides treatment options for 246 supported cases. Real clinical practice were defined as concordant if treatment options were designated "recommended" or "for consideration" by WFO. Concordance of treatment option between WFO and real clinical practice was analyzed statistically. The treatment concordance between WFO and real clinical practice occurred in 72.8% (179/246) of cervical cancer cases. Logistic regression analysis showed that rural registration residences, advanced age, poor ECOG performance status, stages II-IV disease have a remarkable impact on consistency. The main reasons attributed to the 27.2% (67/246) of the discordant cases were the substitution of nedaplatin for cisplatin, reimbursement plan of bevacizumab, surgical preference, and absence of neoadjuvant/adjuvant chemotherapy and PD-1/PD-L1 antibodies recommendations. WFO recommendations were in 72.8% of concordant with real clinical practice for cervical cancer patients in China. However, several localization and individual factors limit its wider application. So, WFO could be an essential tool but it cannot currently replace oncologists. To be rapidly and fully apply to cervical cancer patients in China, accelerate localization and improvement were needed for WFO.