Circular RNA mediator of cell motility 1 (circ-MEMO1) was identified as an oncogene in non-small cell lung cancer (NSCLC). Nevertheless, the working mechanism behind circ-MEMO1-mediated progression of NSCLC is barely known. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-MEMO1, microRNA-101-3p (miR-101-3p), and KRAS protooncogene, GTPase (KRAS). Cell proliferation and aerobic glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and glycolysis detection kits. Flow cytometry was used to evaluate cell cycle progression and apoptosis of NSCLC cells. Western blot assay was used to measure the protein expression of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), KRAS, CD9, CD81, tumor susceptibility 101 (TSG101), and Golgi matrix protein 130 kDa (GM130). The target relationship between miR-101-3p and circ-MEMO1 or KRAS was predicted by StarBase software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay. In vivo tumor growth assay was conducted to assess the effect of circ-MEMO1 in vivo. Exosomes were isolated using the ExoQuick precipitation kit. Circ-MEMO1 was up-regulated in NSCLC, and high expression of circ-MEMO1 predicted poor prognosis in NSCLC patients. Circ-MEMO1 accelerated the proliferation, cell cycle progression, and glycolytic metabolism and inhibited the apoptosis of NSCLC cells. Circ-MEMO1 negatively regulated the expression of miR-101-3p through direct interaction, and si-circ-MEMO1-induced biological effects were attenuated by the introduction of anti-miR-101-3p. MiR-101-3p directly interacted with the 3 untranslated region (3 UTR) of KRAS messenger RNA (mRNA), and KRAS level was regulated by circ-MEMO1/miR-101-3p axis. Circ-MEMO1 silencing suppressed the NSCLC tumor growth in vivo. ROC curve analysis revealed that high expression of serum exosomal circ-MEMO1 (exo-circ-MEMO1) might be a valuable diagnostic marker for NSCLC. Circ-MEMO1 facilitated the progression and glycolysis of NSCLC through regulating miR-101-3p/KRAS axis.

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409 Background: Preoperative chemoradiotherapy before esophagectomy in esophageal squamous cell carcinoma (ESCC) can obtain significant survival benefits for patients compared with surgery alone. The antiangiogenic drugs have shown efficacy in many cancers including esophageal cancer. The benefits of antiangiogenic drugs in neoadjuvant therapy for ESCC still worth exploring. Anlotinib was an effective second-line monotherapy for ESCC in China and the combination of anlotinib and chemotherapy might be a promising strategy as neoadjuvant treatment. Methods: This was a single-arm, non-interventional study. Patients diagnosed stage II-III ESCC confirmed by histopathology would be enrolled(N=30). Patients received neoadjuvant therapy with anlotinib (12 mg, po, d1-14, 21 days per cycle) combined with paclitaxel (135 mg/m2 iv d1, 21 days per cycle) and cisplatin (60-75mg/m2 iv d1, 21 days per cycle). The primary endpoints were pathologic complete response (pCR) rate, rate of R0 resection and disease-free survival (DFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety profile. Results: From July 2020 to September 2022, 20 pts (15 males and 5 females) were enrolled with a median age of 66 years (range: 48-75). 12 pts (60%) had ECOG PS 1, 8 pts had ECOG PS 2. 17/1/2 pts received 2/3/4 cycles of neoadjuvant treatment respectively. In best overall response assessment, ORR was 95% and DCR was 100%. Among them 18 pts underwent esophagectomy and all of them obtained R0 resection, as the rate of R0 resection was 90%. 6 pts (30%) were confirmed to be pCR. The median DFS was not yet available. The safety profile suggested that 3 (15%) pts occurred grade 1-2 treatment-related adverse events (TRAEs), including decreased leukocyte count (5%), diarrhea (5%), nausea and vomiting (5%). No grade ≥3 TRAEs were observed. Conclusions: The preliminary results of this study show promising efficacy and safety of anlotinib combined with paclitaxel and cisplatin as neoadjuvant therapy for patients with esophageal squamous cell carcinoma. More ESCC patients would be recruited in the future. Clinical trial information: ChiCTR2100054374 .