Emerging evidence has validated the vital role of long non‐coding RNA (lncRNA) in the chemoresistance of cancer treatment. In the present study, we investigate the function of lncRNA NR2F1‐AS1 on oxaliplatin (OXA) resistance of hepatocellular carcinoma (HCC) and discover the underlying molecular mechanism. Results revealed that lncRNA NR2F1‐AS1 was up‐regulated in oxaliplatin‐resistant HCC tissue and cells using microarray analysis and RT‐PCR. Meanwhile, ABCC1 protein was overexpressed in OXA‐resistant HCC cells (Huh7/OXA and HepG2/OXA). In vitro, NR2F1‐AS1 knockdown reduced the invasion, migration, drug‐resistant gene (MDR1, MRP5, LRP1) and IC50 value in Huh7/OXA and HepG2/OXA cells. In vivo, NR2F1‐AS1 knockdown decreased the tumour weight of HCC cells. Bioinformatics tools and luciferase reporter assay confirmed miR‐363 targeted the 3′‐UTR of NR2F1‐AS1 and ABCC1 mRNA, presenting that NR2F1‐AS1 promoted ABCC1 expression through endogenous sponging miR‐363. In summary, results conclude that NR2F1‐AS1 regulates HCC OXA resistance through targeting miR‐363‐ABCC1 pathway, providing a vital theoretic mechanism and therapeutic target for HCC chemoresistance.

Our study reveals an unprecedented role of β-catenin in enabling innate immune evasion in CRC.

Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient’s risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.

Our study suggests that IKKε is a potential target to combat CRC induced by aberrant Wnt/β-catenin signalling.

Background Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide, with an overall 5-year survival rate of less than 18%, which may be related to tumor microvascular invasion (MVI). This study aimed to compare the clinical prognosis of HCC patients with or without MVI after radical surgical treatment, and further analyze the preoperative risk factors related to MVI to promote the development of a new treatment strategy for HCC. Methods According to the postoperative pathological diagnosis of MVI, 160 study patients undergoing radical hepatectomy were divided into an MVI-negative group (n = 68) and an MVI-positive group (n = 92). The clinical outcomes and prognosis were compared between the two groups, and then the parameters were analyzed by multivariate logistic regression to construct an MVI prediction model. Then, the practicability and validity of the model were evaluated, and the clinical prognosis of different MVI risk groups was subsequently compared. Result There were no significant differences between the MVI-negative and MVI-positive groups in clinical baseline, hematological, or imaging data. Additionally, the clinical outcome comparison between the two groups presented no significant differences except for the pathological grading (P = 0.002) and survival and recurrence rates after surgery (P < 0.001). The MVI prediction model, based on preoperative AFP, tumor diameter, and TNM stage, presented superior predictive efficacy (AUC = 0.7997) and good practicability (high H-L goodness of fit, P = 0.231). Compared with the MVI high-risk group, the patients in the MVI low-risk group had a higher survival rate (P = 0.002) and a lower recurrence rate (P = 0.004). Conclusion MVI is an independent risk factor for a poor prognosis after radical resection of HCC. The MVI prediction model, consisting of AFP, tumor diameter, and TNM stage, exhibits superior predictive efficacy and strong clinical practicability for MVI prediction and prognostication, which provides a new therapeutic strategy for the standardized treatment of HCC patients.

Background Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis. Methods A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC). Results The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs. Conclusion This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.

Background Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. Methods A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. Results According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value < 0.05). Our novel clinical prediction model was created by based on the above three risk factors and showed superior predictive power in primary cohort (AUC = 0.895) and validation cohort (AUC = 0.863). A nomogram for severe acute pancreatitis in pregnancy (SAPIP) was created based on the three indicators. The nomogram was well-calibrated. Conclusion RDW, NLR and IAP were the independent risk factors of APIP. Our clinical prediction model of severity in APIP based on RDW, NLR and IAP with predictive evaluation is accurate and effective.

Astragaloside IV (AS-IV) or 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcyl-cloastragenol is a bioactive saponin extract from the root of Astragalus membranaceus. It has been proven to have an anti-tumor effect in a variety of tumors by inducing cell apoptosis and inhibiting cell proliferation. Its effects on pancreatic cancer have not been investigated. This study investigated the effects of AS-IV on proliferation, apoptosis and migration of pancreatic cancer cells in vitro and in vivo and explored its underlying mechanism. Pancreatic cancer cell lines SW1990 and Panc-1were treated with different doses of AS-IV. Plate clonality, CCK-8, EDU and flow cytometry were used to explore the effect of AS-IV on pancreatic cancer cell proliferation and cell cycle in vitro. Wound healing was used to investigate the effects of AS-IV on pancreatic cell migration. The protein expression levels of Bax/Bcl2, caspase3/7, cyclin D1, cyclin E and CDK4 were analyzed by western blotting. The results showed that AS-IV significantly inhibited tumor cell proliferation and cell cycle, induced apoptosis both in vitro and vivo on a dose-dependent basis and significantly inhibited the growth of pancreatic cell xenograft tumor in nude mice. Wound healing assays indicated that AS-IV also inhibited the migration of pancreatic cancer cells in a dose-dependent manner. This research confirmed that AS-IV inhibited pancreatic cancer cell proliferation by blocking the cell cycle and inducing apoptosis. It was hypothesized from this experiment that the potential mechanism of AS-IV inducing apoptosis of pancreatic cancer cells may be understood by activating the Bcl2/Bax/Caspase-3/Caspase-7 signaling pathway.