Helicobacter pylori CagA promotes immune evasion of gastric cancer by upregulating PD-L1 level in exosomes.

Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

Evaluation of early liquid drinking after radical gastrectomy in gastric cancer: a Chinese multicenter propensity score matching analysis.

Background: Enhanced recovery after surgery is used in gastrointestinal surgery. This study aimed to access the effects of early liquid drinking (ELD) on gastrointestinal function recovery in patients with gastric cancer (GC) who underwent radical gastrectomy, as high-quality evidence on the outcomes of ELD after gastrectomy is currently lacking. Methods: Clinicopathological data of patients with GC from 11 centers were retrospectively analysed. Clinical outcomes were investigated in 555 patients, including 225 who started drinking liquid within 48 h (ELD group) of surgery and 330 who started drinking liquid after flatus resumption (traditional liquid drinking [TLD] group). Propensity score matching (PSM) analysis was performed using a match ratio of 1:1 and 201 patients were selected from each group for the analysis. Primary outcome was time to first passage of flatus. Secondary outcomes included time to first defecation, post-operative hospitalization days, occurrence of short-term post-operative complications, and hospitalization costs. Results: After PSM, baseline characteristics were not significantly different between the two groups. The time to first flatus (2.72 ± 1.08 vs 3.36 ± 1.39 days), first defecation (4.34 ± 1.85 vs 4.77 ± 1.61 days), and post-operative hospital stay (8.27 ± 4.02 vs 12.94 ± 4.43 days) were shorter in the ELD group than in the TLD group (all P < 0.05). The ELD group had lower hospitalization costs than the TLD group ([7.83 ± 2.44 vs 8.78 ± 3.41] × 104 RMB, P = 0.041). No significant differences were observed in the incidence of post-operative complications. Conclusions: Compared with TLD, post-operative ELD could promote rapid recovery of gastrointestinal function and reduce hospitalization costs; moreover, ELD does not increase the risk of post-operative complications.

Multimodal Imaging of Target Detection Algorithm under Artificial Intelligence in the Diagnosis of Early Breast Cancer.

This study aimed to analyze the diagnostic value of multimodal images based on artificial intelligence target detection algorithms for early breast cancer, so as to provide help for clinical imaging examinations of breast cancer. This article combined residual block with inception block, constructed a new target detection algorithm to detect breast lumps, used deep convolutional neural network and ultrasound imaging in diagnosing benign and malignant breast lumps, took breast density grading with mammography, compared the convolutional neural network (CNN) algorithm with the proposed algorithm, and then applied the proposed algorithm to the diagnosis of 120 female patients with breast lumps. According to the results, accuracy rates of breast lump detection (94.76%), benign and malignant breast lumps diagnosis (98.22%), and breast grading (93.65%) with the algorithm applied in this study were significantly higher than those (75.67%, 87.23%, and 79.54%) with CNN algorithm, and the difference was statistically significant (P < 0.05); among 62 patients with malignant breast lumps of the 120 patients with breast lumps, 37 were patients with invasive ductal carcinoma, 8 with lobular carcinoma in situ, 16 with intraductal carcinoma, and 4 with mucinous carcinoma; among the remaining 58 patients with benign breast lumps, 28 were patients with fibrocystic breast disease, 17 with intraductal papilloma, 4 with breast hyperplasia, and 9 with adenopathy; the differences in shape, growth direction, edge, and internal echo of multimodal ultrasound imaging of patients with benign and malignant breast lumps had statistical significance (P < 0.05); the malignant constituent ratios of patients with breast density grades I to IV were 0%, 7.10%, 80.40%, and 100%, respectively. In short, the multimodal imaging diagnosis under the algorithm in this article was superior to CNN algorithm in all aspects; according to the judgment on benign and malignant breast lumps and breast density with multimodal imaging features, the higher the breast density, the higher the probability of breast cancer.

Risk Factors of Lymph Node Metastasis and Its Prognostic Significance in Early Gastric Cancer: A Multicenter Study.

BACKGROUND: Early gastric cancer (EGC) is invasive gastric cancer that invades no deeper than the submucosa, regardless of lymph node metastasis (LNM). It is mainly treated by surgery. Recently, the resection range of EGC has been minimized, but cancer recurrence and overall survival in some patients should be given high status. LNM is an important indicator of prognosis and treatment in gastric cancer. The law of the number and location of metastatic lymph nodes in EGC is not yet clear. Therefore, we aimed to identify the risk factors of LNM in radically resected EGC and guide treatment. METHODS: The clinicopathological factors of 611 patients with EGC were retrospectively analyzed in six hospitals between January 2010 and December 2016. The relationship between clinicopathological factors and LNM, as well as their prognostic significance, were analyzed by univariate and multivariate analyses. RESULTS: The rate of LNM was 20.0% in the 611 EGC patients. The depth of invasion, differentiation type, tumor diameter, morphological ulceration, and lymphovascular invasion were independent risk factors for LNM (P<0.05) by logistic regression analysis. Tumor location in the proximal third of the stomach and morphological ulceration were significant factors for group 2 LNM. Moreover, the 5-year survival rate was 94.9% for patients with no positive nodes, 88.5% for patients with 1-2 positive nodes, 64.3% for patients with 3-6 positive nodes, and 41.8% for patients with >6 metastatic nodes. Interestingly, the 7-year risk of relapse diminished for patients with no LNM or retrieved no less than 15 lymph nodes. CONCLUSIONS: Fifteen lymph node dissection and D2 radical operation are the surgical options in case of high risk factors for LNM. Extended lymph node dissection (D2+) is recommended for morphological ulceration or disease located in the proximal third of the stomach due to their high rate of group 2 LNM. Furthermore, LNM is a significant prognostic factor of EGC. Moreover, lymph nodes can also play a significant role in the chemotherapeutic and radiotherapy approach for non-surgical patients with EGC.

The effect of Helicobacter pylori eradication on prognosis of postoperative early gastric cancer: a multicenter study.

OBJECTIVE: To investigate the effect of Helicobacter pylori (H. pylori) eradication on the prognosis of postoperative early gastric cancer (EGC). METHODS: This is a retrospective study based on data from 6 hospitals. We identified 429 patients with EGC who underwent curative gastrectomy from January 2010 to December 2016. All of the patients were tested for H. pylori. Patients were divided into two groups, the successful H. pylori eradication group (group A, 268 patients) and the non-H. pylori eradication group (group B, 161 patients), for calculating the disease-free survival (DFS) and overall survival (OS) of each group. RESULT: Positive node metastasis (hazard ratio (HR), 3.13; 95% confidence interval (CI), 1.84-5.32; P < 0.001), undifferentiated type (HR, 2.54; 95% CI, 1.51-4.28; P < 0.001), and non-H. pylori eradication (HR, 1.73; 95% CI, 1.08-2.77; P = 0.023) were statistically significantly independent risk factors of recurrence. Patient's age ≥60 years old (HR, 3.32; 95% CI, 2.00-5.53; P < 0.001), positive node metastasis (HR, 3.71; 95% CI, 2.25-6.12; P < 0.001), undifferentiated type (HR, 3.06; 95% CI, 1.79-5.23; P < 0.001), and non-H. pylori eradication (HR, 1.83; 95% CI, 1.11-3.02; P = 0.018) were statistically significantly independent risk factors of overall survival. CONCLUSION: H. pylori eradication treatment could prevent the recurrence of postoperative EGC to prolong the overall survival of patients with EGC.

A Novel Mechanism of the c-Myc/NEAT1 Axis Mediating Colorectal Cancer Cell Response to Photodynamic Therapy Treatment.

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124-mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

Role of robotic natural orifice specimen extraction surgery in colorectal neoplasms.

Natural orifice specimen extraction surgery (NOSES) is especially suitable for colorectal surgery. Until now, most of the reports published were about laparoscopic NOSES, the reports about robotic NOSES are extremely rare. This study aims to explore the safety and feasibility of robotic NOSES for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data including patient characteristics, perioperative information and pathological information were collected and analyzed. According to the distance between tumor and anus or whether neoadjuvant chemoradiotherapy (nRCT) is performed, we grouped the cases and studied its influence on robotic NOSES. Also, we compared the previous reports on laparoscopic NOSES with our study and revealed advantages of robotic NOSES in terms of safety and feasibility. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.

circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis.

Pancreatic cancer (PC) is one of the most common and lethal cancers that affects millions of people around the world. The prognosis of PC is poor with very limited effective treatments. Here, we fully investigated the function and underlying mechanism of circSFMBT1 (hsa_circ_0066147) in PC. Real-time quantitative PCR, Western blotting, and immunohistochemistry were used to examine levels of circSFMBT1, miR-330-5p, PAK1 (p21-activated kinase 1), or proliferation/metastasis-related proteins. Colony formation assay, flow cytometry, and transwell assay detected the roles of circSFMBT1 and miR-330-5p in cell apoptosis, proliferation, migration, and invasion of PC cells, respectively. Dual luciferase assay and RNA immunoprecipitation were used to validate the interactions of circSFMBT1/miR-330-5p and miR-330-5p/PAK1. Fluorescence in situ hybridization was performed to examine the subcellular localization of circSFMBT1 and miR-330-5p. Subcutaneous tumor growth was monitored in nude mice and in vivo metastasis was examined as well following injection of PC cells into the tail vein. This study demonstrated that circSFMBT1 and PAK1 were up-regulated in PC tissues and cells, while miR-330-5p was down-regulated. circSFMBT1 directly bound miR-330-5p and inhibited its expression. In addition, circSFMBT1 promoted proliferation, migration, and invasion of PC cells through up-regulating proliferation-related proteins and down-regulating apoptosis-related proteins via miR-330-5p. miR-330-5p directly bound PAK1 mRNA and suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition process via targeting PAK1 in PC cells. Further, knockdown circSFMBT1 increased miR-330-5p level, but decreased PAK1 expression and repressed tumor growth and metastasis in vivo. Taken together, circSFMBT1 promotes proliferation and metastasis of PC via regulating miR-330-5p/PAK1 pathway as a miR-330-5p sponge.

Safety and Feasibility of Robotic Natural Orifice Specimen Extraction Surgery in Colorectal Neoplasms During the Initial Learning Curve.

Aim: To analyze the learning curve (LC) for robotic natural orifice specimen extraction surgery (NOSES) for colorectal neoplasms and evaluate safety and feasibility during the initial LC. Method: Patients who consecutively underwent robotic NOSES performed by two surgeons between March 2016 and October 2019 were analyzed retrospectively. The operation time was evaluated using the cumulative sum method to analyze the LC. The clinicopathological data before and after the completion of LC were extracted and compared to evaluate safety and feasibility. Results: In total, 99 and 66 cases were scheduled for robotic NOSES by Prof. Yao and Prof. Li, respectively. The peak points of LC were observed at the 42nd and 15th cases of Yao and Li, respectively, then operation time began to decrease. Only the operation time for Yao before the completion of LC (213.3 ± 67.0 min) was longer than that after the completion of LC (143.8 ± 33.3 min). For Yao nor for Li, other indices, such as postoperative hospital stay, intraoperative blood loss, conversion to laparotomy, incidence of anastomotic leakage, reoperation rate, and 90-day mortality rate lacked significant statistical differences(P > 0.05). In terms of feasibility, the number of lymph nodes harvested, positive resection margin rate, and total cost before and after the completion of LC had no significant statistical difference (P > 0.05). Conclusion: The cases before the completion of LC for robotic NOSES in colorectal neoplasms varied from 15 cases to 42 cases. Robotic NOSES is safe and feasible during the initial LC.

Totally Robotic Distal Gastrectomy: A Safe and Feasible Minimally Invasive Technique for Gastric Cancer Patients Who Undergo Distal Gastrectomy.

PURPOSES: To explore the safety and feasibility of totally robotic distal gastrectomy (TRDG) for gastric cancer patients who undergo distal gastrectomy. METHODS: Consecutive patients with gastric cancer who underwent TRDG (TRDG group) and robotic-assisted distal gastrectomy (RADG) (RADG group) were systematically reviewed at the Second Xiangya Hospital of Central South University from October 2015 to August 2018. Data were collected and statistically analyzed. RESULTS: A total of 161 consecutive patients were included in this study: 84 cases in the TRDG group and 77 in the RADG group. Clinical characteristics and pathological results were mostly similar in both groups. The TRDG group had a significantly longer anastomotic time (20.6 ± 3.3 vs. 17.5 ± 4.0 min, p ˂ 0.001) but showed no difference in total operating time (167.0 ± 18.0 vs. 162.9 ± 17.6 min, p = 0.159). The postoperative hospitalization in the TRDG group was shorter than that in the RADG group (6.7 ± 1.2 vs. 7.2 ± 1.7 days, p = 0.019). Conversion rate, estimated blood loss, and postoperative complications were similar in both groups. There were no statistical differences in the estimated 2-year disease-free survival and overall survival rate between both groups. CONCLUSIONS: Although our current results need to be verified in further studies, TRDG represents a safe and feasible approach to distal gastrectomy and embodies the theory of minimally invasive surgery.

Inhibitory Effect and Molecular Mechanism of the New Phorphyrin-Based HCE6 Photosensitizer on the Activity of MKN45 Human Gastric Cancer Cells.

Gastric cancer is the fourth most common cancer worldwide and the third most common in Asia, with a high mortality. Photodynamic therapy (PDT) is a new treatment for cancer. With advantages of minimum invasiveness, small adverse side effects and high selectivity, PDT can be used as palliative treatment for patients with advanced gastric cancer. YLG I, also known as 2-(1 hexyloxyethyl)-2-devinyl porphin e6 trisodium salt (HCE6), is a recently developed photosensitizer. A previous study showed that HCE6 significantly inhibited the growth of QBC939 human cholangiocarcinoma cells. However, the effects and mechanisms of HCE6 on gastric cancer cell suppression are not known. In this study, we investigated the effects of HCE6 on the human gastric cancer cell line MKN45 and found that at the concentration of 2.0 mg/L, HCE6 almost completely killed MKN45 cells at a light intensity of 3.6 J/cm². RNAseq results confirmed that mitochondria and endoplasmic reticulum (ER)-mediated apoptosis was involved in the effects of HCE6 on cell death, and we also found that HCE6 induced chromosome conformational changes in the early phase of apoptosis. The results of our study help elucidate the molecular mechanisms underlying HCE6-mediated inhibition of gastric cancer cell growth and provide a theoretical basis and molecular targets for the treatment of gastric cancer.

Photodynamic therapy as salvage therapy for residual microscopic cancer after ultra-low anterior resection: A case report.

BACKGROUND: The rate of positive resection margins (R1) in patients with low rectal cancer is substantial. Recommended remedies such as extended resection or chemoradiotherapy have their own serious drawbacks. It has been reported that photodynamic therapy (PDT) as a remedial treatment for esophageal cancer. Colorectal cancer and esophageal cancer has many similarities, however, PDT as a salvage therapy for rectal cancer is rare. CASE SUMMARY: Here, we describe a 56-year-old man who was admitted to the hospital due to a 6-mo history of hemafecia, which had been aggravated for 1 mo. Colonoscopy revealed a 3 cm × 4 cm ulcerated mass in the rectum 4 cm from the anus. Preoperative pathological examination showed villous adenoma, moderate-to-high-grade dysplasia, good differentiation, and invasion of the mucosal muscle. The patient had R1 after ultra-low anterior resection, but he refused extended resection and experienced severe liver function impairment after 3 cycles of chemotherapy. Ultimately, the patient underwent PDT to remove R1. After five years of follow-up, there was no liver function impairment, recurrence, metastasis, sexual dysfunction, or abnormal defecation function. CONCLUSION: This is the first case worldwide in which R1 of rectal cancer were successfully treated by PDT.

Downregulation of the Helicase Lymphoid-Specific (HELLS) Gene Impairs Cell Proliferation and Induces Cell Cycle Arrest in Colorectal Cancer Cells.

AIM: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer worldwide. Despite the decrease in mortality of CRC patients, further investigation of the molecular pathogenesis of CRC could unveil new therapeutic targets and offer better prognosis predictions, which might direct attention to epigenetic regulators. METHODS: Publicly available data from the Gene Expression Omnibus (GEO) database and clinical samples were collected. Bioinformatics methods were used to screen hub genes expressed in CRC. qRT-PCR and Western blotting were used to experimentally determine the expression of one gene of interest, the helicase lymphoid-specific (HELLS) gene, at the RNA and protein levels. Immunohistochemical (IHC) assays were used to correlate the stained HELLS proteins to survival data. Cell proliferation levels were assayed by a CCK-8 kit, a colony formation assay was performed, and flow cytometry was used to quantify the cells at each stage of the cell cycle. RESULTS: A total of 225 overlapping genes were screened, including 14 hub genes. Analysis through a protein-protein interaction (PPI) network and the Gene Ontology database was performed by using the Cytoscape and DAVID online tools, respectively. HELLS RNA and protein expression levels in tumor tissues were 2.09-fold higher and 1.46-fold higher, respectively, than in the peritumoral tissues (p < 0.001, p<0.001). HELLS expression was significantly associated with the T stage (p=0.0027), M stage (p=0.0119), and TNM clinical stage (p = 0.0312) and a higher pathological grade (p=0.049). Highly expressed HELLS was reversibly associated with overall survival (log-rank p = 0.027). HELLS siRNA impaired cell proliferation and colony generation in vitro. HELLS siRNA induced significant G2+M arrest in HT29 and HCT116 cells compared with the respective negative controls (82.29% vs 25.85% and 35.41% vs 15.26%, respectively). CONCLUSION: Our data revealed that HELLS was significantly upregulated in CRC and correlated with clinicopathological parameters. High expression of HELLS indicated poor prognosis for CRC patients. HELLS knockdown led to impaired cell proliferation, colony generation, and G2+M cell cycle arrest.

GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF-κB signaling pathway in colorectal cancer cells.

GNA13 has been found overexpressed in various types of cancer, which is related to tumor metastasis and progression. However, the biological functions of GNA13 in colorectal cancer (CRC) progression remain unclear. This study aimed to explore the role of GNA13 in CRC and investigate the mechanism of how GNA13 promotes tumor growth. Interestingly, our findings showed that GNA13 is commonly upregulated in CRC, where these events are associated with a worse histologic grade and poor survival. Increased expression levels of GNA13 promoted cell growth, migration, invasion, and epithelial-mesenchymal transition, whereas GNA13 silencing abrogated these malignant phenotypes. In addition, overexpressing GNA13 in cancer cells increased the levels of the chemokines CXCL1, CXCL2, and CXCL4, which contributed to CRC proliferation and colony formation. Moreover, our mechanistic investigations suggest that the NF-κB/p65 signaling pathway was activated by the increase in GNA13 levels. Inhibiting the NF-κB/p65 pathway with an inhibitor decreased GNA13-induced migration, invasion and CXCL chemokine level increases, indicating the critical role of NF-κB/p65 signaling in mediating the effects of GNA13 in CRC. Together, these results demonstrate a key role of GNA13 overexpression in CRC that contributes to malignant behavior in cancer cells, at least in part through stimulating angiogenesis and increasing the levels of the NF-κB-dependent chemokines CXCL1, CXCL2, and CXCL4.

Robotic low anterior resection plus transanal natural orifice specimen extraction in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis (SIT) refers to an unusual condition involving reversal of abdominal and thoracic viscera, with an incidence rate of 1/5000-20,000 adults. Minimally invasive surgeries for SIT patients are technically challenging, while the surgical experience for SIT patients is quite limited. CASE PRESENTATION: A 61-year-old man, previously diagnosed as SIT, came to our hospital for 6 months history of hematochezia and altered bowel habit. A diagnosis of rectal cancer was made in view of colonoscopic biopsy which confirmed an irregular circumferential lump of well differentiated adenocarcinoma at 10 cm from the anal verge. The computed tomography contrast-enhanced (thorax + abdomen + pelvis) scan revealed a total transposition of abdominal and thoracic organs and an enhanced eccentric mass of rectal but with no evidence of distant metastasis. Robotic low anterior resection (LAR) plus transanal natural orifice specimen extraction (NOSE) was performed after obtaining informed consent. The procedure was performed successfully and the patient convalesced nicely without any complications. The postoperative pathological diagnosis revealed a 4x4x0.6 cm3 moderately differentiated adenocarcinoma and circumferential clearance. CONCLUSIONS: Robotic LAR plus transanal NOSE for rectal cancer patients with SIT can be performed safely and may be an effective approach in contrast to open or laparoscopic approach, despite the unconventional anatomy.

Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy.

Colorectal Cancer (CRC) is one of the most common digestive system malignant tumors. Recently, PDT has been used as a first-line treatment for colon cancer; however, limited curative effect was obtained due to resistance of CRC to PDT. During the past decades, accumulating CRC-related long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs have been reported to exert diverse functions through various biological processes; their dysregulation might trigger and/or promote the pathological changes. Herein, we performed microarrays analysis to identify dysregulated lncRNAs, miRNAs and mRNAs in PDT-treated HCT116 cells to figure out the lncRNA-miRNA interactions related to the resistance of CRC to PDT treatment, and the downstream mRNA target, as well as the molecular mechanism. We found a total of 1096 lncRNAs dysregulated in PDT-treated CRC HCT116 cells; among them, LIFR-AS1 negatively interacted with miR-29a, one of the dysregulated miRNAs in PDT-treated CRC cells, to affect the resistance of CRC to PDT. LIFR-AS1 knockdown attenuated, whereas miR-29a inhibition enhanced the cellular effect of PDT on HCT116 cell proliferation and apoptosis. Furthermore, among the dysregulated mRNAs, TNFAIP3 was confirmed to be a direct target of miR-29a and exerted a similar effect to LIFR-AS1 on the cellular effects of PDT. In summary, LIFR-AS1 serves as a competitive endogenous RNA (ceRNA) for miR-29a to inhibit its expression and up-regulate downstream target TNFAIP3 expression, finally modulating the resistance of CRC to PDT. We provide an experimental basis for this lncRNA/miRNA/mRNA network being a promising target in CRC resistance to PDT treatment.

Wild-type and mutant p53 differentially modulate miR-124/iASPP feedback following pohotodynamic therapy in human colon cancer cell line.

Colorectal cancer (CRC) is a most common digestive system malignant tumor. p53 mutation has essential role in cancers and is frequently observed in CRC and presents a huge challenge. p53 mutation has been reported to attenuate the inhibitory effect of photofrin-based photodynamic therapy (PDT). p53 mutation-induced gain of function brings up the dysfunction of carcinogenic factors, including miRNAs. Our research found that PDT suppressed CRC cell viability, reduced the tumor size and prolonged the survival time, all of which could be attenuated by p53 mutation or deletion. After p53 mutation or deletion, several miRNA expression levels were downregulated, among which miR-124 was the most strongly downregulated, whereas iASPP expression was upregulated. p53 binds to the promoter of miR-124 to promote its expression and then inhibited iASPP expression, so as to amplify the inhibitory effect of PDT on wild-type p53 cells. In p53-mutant or -deleted cells, this binding no longer worked to promote miR-124 expression, and iASPP expression increased, finally resulted in promoted CRC cell viability upon PDT. The interactive modulation among miR and iASPP in p53-mutant or -deleted cells may serve as a crucial pathway, which mediates therapy resistance when p53 is mutated or deleted, in the process of PDT treatment of CRC.

The miR-124-p63 feedback loop modulates colorectal cancer growth.

Among the diverse co-regulatory relationships between transcription factors (TFs) and microRNAs (miRNAs), feedback loops have received the most extensive research attention. The co-regulation of TFs and miRNAs plays an important role in colorectal cancer (CRC) growth. Here, we show that miR-124 can regulate two isoforms of p63, TAp63 and ΔNp63, via iASPP, while p63 modulates signal transducers and activators of transcription 1 (STAT1) expression by targeting miR-155. Moreover, STAT1 acts as a regulator of CRC growth by targeting miR-124. Taken together, these results reveal a feedback loop between miRNAs and TFs. This feedback loop comprises miR-124, iASPP, STAT1, miR-155, TAp63 and ΔNp63, which are essential for CRC growth. Moreover, this feedback loop is perturbed in human colon carcinomas, which suggests that the manipulation of this microRNA-TF feedback loop has therapeutic potential for CRC.

[Inhibitory effect of jianpi-jiedu prescription-contained serum on colorectal cancer SW48 cell proliferation by mTOR-P53-P21 signalling pathway].

OBJECTIVE: To investigate the effect of jianpi-jiedu (JPJD) prescription-contained serum on colorectal cancer SW48 cell proliferation and the underlying mechanisms.
 Methods: Crude extract from JPJD was made by water extract method and the main components of crude extract from JPJD were analyzed by ultra-performance liquid phase high resolution time of flight mass spectrometry (UPLC-Q-TOF/MS). The low, medium, and high-concentration of JPJD-contained serum were prepared by the serum pharmacological method. The effect of serum containing JPJD on SW48 cell proliferation was determined by MTT assay. The cell cycle was detected by flow cytometric method. The protein levels of mammalian target of rapamycin (mTOR), phospho-mTOR, P-P53, and -P21, and the mRNA level of mTOR were examined by Western blot and RT-PCR, respectively.
 Results: Seven compounds including calycosin-7-glucoside, astragaloside, ginsenoside-Re, ginsenoside-Rb1, glycyrrhizinic acid, apigenin, atractylenolide-II were identified. MTT assays demonstrated that the SW48 cell proliferation was inhibited by medium and high concentration of JPJD-contained serum and the percentages of cells at G1 phase in SW48 cell cultured in the medium and high concentration of JPJD serum group were significantly higher than those in the control group (P<0.05). Meanwhile, the levels of mTOR mRNA and phospho-mTOR protein in the medium and high concentration of JPJD serum groups were substantially lower than those in the control group (P<0.05). Conversely, the expressions of phospho-P53 and P21 protein were significantly increased in the medium and high concentration of JPJD serum group compared with those in the control group.
 Conclusion: JPJD prescription-contained serum can inhibit SW48 cell proliferation, which may be related to mTOR-P53-P21 signaling pathways.