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BACKGROUND Colorectal mucinous adenocarcinoma is a distinct subtype of colorectal adenocarcinoma that is not sensitive to chemotherapy and radiotherapy, and its prognosis is worse than that of nonmucinous adenocarcinoma. Early diagnosis and aggressive surgical treatment may be the key to improving the prognosis of patients. Ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess caused by non-intestinal perforation has never been reported. Moreover, since the lumen of the ascending colon is large, and early stage ascending colon cancer lacks typical clinical manifestations, the diagnosis may be delayed easily. We herein report three cases of delayed diagnosis of colorectal mucinous adenocarcinoma. CASE SUMMARY We present three patients (two females and one male) with mucinous ascending colon mucinous adenocarcinoma with the primary manifestation of a local abscess (the right area of the lumbar spine, right groin, and lower right abdomen) caused by non-intestinal perforation. At the initial clinical visit, the common causes of those abscesses, including spinal tuberculosis and urinary tract infection, were excluded. The treatment of the abscess was through an incision and drainage. However, the source of the abscess was not made clear, which led to an abscess recurrence and a delayed diagnosis of colorectal mucinous adenocarcinoma. After the patients were referred to our hospital, a definitive diagnosis of ascending colon mucinous adenocarcinoma was made with the help of tumor markers and colonoscopic findings. Because of the delayed diagnosis of the disease, two patients (case 1 and case 2) missed the chance of surgery due to disease progression and died in a short follow-up period. Only case 3 underwent radical surgery for the tumor in the right colon and partial abdominal wall resection and achieved a better prognosis. CONCLUSION Abscesses in the right area of the lumbar spine, right groin, or right lower quadrant caused by non-intestinal perforation as the primary clinical manifestation of ascending colon mucinous adenocarcinoma are extremely rare. Mucinous adenocarcinoma of the ascending colon may be one of the causes of such abscesses. Performing colonoscopy as soon as possible is of great significance in the diagnosis and treatment of the disease.

Cancer stem cells (CSCs) are the main cause of tumor generation, recurrence, metastasis, and therapy failure in various malignancies including colorectal cancer (CRC). Accumulating evidence suggests that tumor cells can acquire CSC characteristics through the epithelial-mesenchymal transition (EMT) process. However, the molecular mechanism of CSCs remains unclear. OCT4B1 is a transcript of OCT4, which is initially expressed in embryonic stem and carcinoma cells, and is involved in the regulation and maintenance of an undifferentiated state of stem cells. In this study, three-dimensional (3D) microspheres were confirmed as CRC stem cells. Compared with that of parental cells, their self-renewal ability was significantly increased, and OCT4B1 expression was increased and promoted the EMT process. The knockdown of OCT4B1 decreased the self-renewal of CSCs and reversed EMT. Moreover, OCT4B1 induced the expression of Polo-like kinase 1 (PLK1), which is a key regulator of EMT in tumor cells. Further examination showed that OCT4B1 regulated the miR-8064/PLK1 balance to exert its function. Taken together, our data suggest that OCT4B1 may be involved in regulating the self-renewal of colorectal CSCs through EMT, which is at least partially due to the miR-8064/PLK1 balance. This study indicates that OCT4B1 is a potential therapeutic target for CRC by targeting CSCs. Keywords: OCT4B1, EMT, cancer stem cell, colorectal cancer, self-renewal, PLK1, miR-8064

Long non-coding RNAs (lncRNAs) fulfill important roles in the majority of cellular processes. Previous studies have demonstrated that lncRNAs are involved in the pathogenesis of various diseases, including cancer. However, to date, the functions of only a small number of the known lncRNAs have been well-documented. lncRNAs comprise a class of multifunctional non-coding transcripts that are able to interact with different types of biomolecules. Interactions between lncRNAs and RNA-binding proteins (RBPs) provide an important mechanism through which lncRNAs exert their regulatory functions, mainly through findings on ‘generalized RBPs’. Regulatory effects on lncRNAs mediated by RBPs have also been explored. Taking account of the research that has been completed to date, the continued and in-depth study of the bidirectional interactions between lncRNAs and RBPs will prove to be of major importance for understanding the pathogenesis of cancer and for developing effective therapies. The present review aims to explore the interactions between lncRNAs and RBPs that have been investigated in cancer, taking into consideration several different aspects, including the regulation of expression, subcellular localization and the mediation of diverse functions.

The presence of cancer stem cells (CSCs) is a major cause of therapeutic failure in a variety of cancer types, including colorectal cancer (CRC). However, the underlying mechanisms that regulate the self‑renewal of colorectal cancer stem cells (CRCSCs) remain unclear. Our previous study utilized CRCSCs and their parent cells; through gene microarray screening and bioinformatics analysis, we hypothesized that microRNA (miR)‑8063 may bind to, and regulate the expression of, heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) to facilitate the regulation of CRCSC self‑renewal. The aim of the present study was to confirm this conjecture through relevant experiments. The results indicated that compared with that in parent cells, miR‑8063 expression was significantly downregulated in CRCSCs, while hnRNPAB expression was increased. Furthermore, hnRNPAB was identified as a direct target of miR‑8063 using a dual‑Luciferase assay. Overexpression of hnRNPAB promoted the acquisition of CSC characteristics in CRC cells (increased colony formation ability, enhanced tumorigenicity, and upregulated expression of CSC markers), as well as the upregulation of key proteins (Wnt3a, Wnt5a and β‑catenin) in the Wnt/β‑catenin signaling pathway. Similarly, after silencing miR‑8063 in CRC cells, the characteristics of CSC were altered, and the expression of hnRNPAB protein was promoted. However, post overexpression of miR‑8063 in CRCSCs, the self‑renewal ability of CSCs was weakened with the downregulation of hnRNPAB protein, Wnt3a, Wnt5a and β‑catenin. These results suggest that as a tumor suppressor, miR‑8063 is involved in regulating the self‑renewal of CRCSCs, where loss of miR‑8063 expression weakens its inhibition on hnRNPAB, which leads to the activation of Wnt/β‑catenin signaling to promote the self‑renewal of CRCSCs.

Background: Gastrointestinal stromal tumor (GIST) is the most common stromal tumor of the gastrointestinal tract and it is considered to be an aggressive tumor with potentially malignant tendency. GIST is a tumor derived from mesenchymal tissue of the gastrointestinal tract or rarely of intraperitoneal soft tissue. Stem cajal cells from the muscular layer of the digestive tract are the precursor cells of GIST, which are pacemaker cells that cause the intestinal peristalsis and contract. The etiology of GIST is mainly caused by mutations in the KIT or PDGFRA oncogene. Although some papers reported that inflammation can cause tumor formation, it has not been reported that inflammation can cause GIST formation.Case presentation: A 64-year-old male patient was evaluated for recurrent dull pain and discomfort in the left upper abdomen. He had a history of abdominal trauma approximately six years prior. During this period, abdominal pain and fever were intermittent recurrent attacked. Intraoperative jejunum tumors were found to have inflammatory packages. Postoperative pathological examinations showed that the tumor envelope was intact and a large amount of inflammatory cells were seen around the tumor cells. Histopathology of the resected masses was positive for CD117 and Dog-1, and the patient was diagnosed as jejunum GIST.Conclusion: We reported a case of gastrointestinal stromal tumor that may be caused by repeated stimulation of chronic inflammation that caused by trauma. Early detection and timely removal of the inducement of repeated chronic inflammation can effectively prevent the occurrence of GIST.

Heterogeneous ribonucleoprotein AB (hnRNP AB) is a member of the heterogeneous nuclear ribonucleoprotein family, which serves important functions in gene expression and signal transduction. However, the expression and clinicopathological significance of hnRNP AB in colorectal cancer (CRC) remain to be elucidated. To investigate the expression and clinical significance of hnRNP AB in CRC, hnRNP AB expression levels were analysed in two independent cohorts of patients with CRC. The results of reverse transcription-quantitative PCR, immunohistochemistry and western blot analysis demonstrated that hnRNP AB was upregulated in CRC tissues compared with the corresponding adjacent normal tissues. Immunohistochemical analyses indicated that a high expression of hnRNP AB was significantly associated with preoperative carcinoembryonic antigen (CEA; P

Objective To explore whether the enrichment of cancer stem cells (CSCs) in colorectal cancer by suspension culture method is involved with epithelial-mesenchymal transition (EMT). Methods 3D microspheres were cultured by suspension culture method to human colorectal cancer SW620 cells. The 3D microspheres and SW620 cells were used as the research objects. To clarify whether 3D microspheres were enriched with CSCs, we made tumorigenicity experiments in NOD/SCID mice, soft agar cloning experiments, and detected the expression levels of cancer stem cells markers CD44 and Ep-CAM by flow cytometry or by Western blotting. The protein expression levels of EMT markers such as E-cadherin, N-cadherin and vimentin were detected by Western blotting. Results Compared with the parental SW620 cells, colony formation in vitro (P

OCT4B1, a splice variant of OCT4, is a key regulator in maintaining the properties of pluripotency and self-renewal in embryonic stem (ES) cells. Recent results have shown that OCT4B1 is involved in tumorigenesis. However, the contribution of OCT4B1 in the tumorigenesis and drug resistance of colon cancer remains to be determined. The aim of the present study was to determine whether OCT4B1, which maintains the stemness of ES cells, promoted cell growth by facilitating transition of the cell cycle and reduced apoptosis in colon cancer and drug‑resistant cells using flow cytometry and western blotting. The results showed that, OCT4B1 promoted the growth of colon cancer and drug‑resistant cancer cells by maintaining the activity of ES cells and by facilitating the transition of the cell cycle and reducing apoptosis. Additionally, OCT4B1 was able to reduce sensitivity to oxaliplatin by altering the expression of two important mediators in drug resistance, P-gp and ABCG2 [ATP-binding cassette, sub‑family G (WHITE), member 2]. Furthermore, OCT4B1 enhanced the ability of migration and invasion through alteration of the epithelial-to-mesenchymal transition (EMT) in colon cancer. In conclusion, to the best of our knowledge, the results demonstrated for the first time that OCT4B1 functions as an oncogene in colon cancer and provides the development of novel therapeutic strategies to treat colon cancer, particularly drug resistance.

Colorectal cancer is one of the most common alimentary malignancies. Slug has been shown to be an ideal target for cancer gene therapy by numerous studies due to its strong anti‑apoptotic effect. The elevated expression of Slug is a frequent genetic abnormality observed in colorectal cancer. In the present study, a Slug short hairpin RNA (shRNA) expression vector that was able to efficiently inhibit the expression of Slug in HCT116 cells was prepared. Following transfection, the mRNA expression levels were detected by RT‑PCR analysis. Western blotting detected a similar inhibition of the Slug protein levels in the cells transfected with the pGCsi‑Slug plasmid. Downregulation of Slug resulted in a significant inhibition of cancer cell growth in vitro. Cell invasion and apoptosis were decreased concomitantly with the reduction in Slug protein expression. These results suggested that RNA interference (RNAi) was able to downregulate the Slug protein level in HCT116 cells and significantly inhibit tumor growth in vitro. These findings suggest that RNAi has therapeutic potential for the treatment of colorectal cancer, as well as other types of cancer, by targeting the overexpression of oncogenes, including Slug.

Objective To investigate the expression of Cripto-1 in esophageal carcinoma and its relationship with epithelial-mesenchymal transformation (EMT). Methods RT-PCR and Western blotting were used to examine the expression levels of Cripto-1 in carcinoma, paraneoplastic and normal esophageal mucosa tissue of 41 patients with esophageal carcinoma. The protein expressions of Cripto-1 and EMT markers such as N-cadherin, Vimentin and E-cadherin were detected by immunohistochemistry, and the clinical pathologic parameters were simultaneously analyzed. The correlation between Cripto-1 and the expression of N-cadherin, Vimentin and E-cadherin were also analyzed. Results The expression levels of Cripto-1 mRNA and protein were significantly higher in esophageal carcinoma (0.35±0.08 and 0.62±0.06) than in paraneoplastic (0.22±0.04 and 0.45±0.07) and normal esophageal mucosa tissue (0.13±0.03 and 0.33±0.05, P

Objective To investigate the effect of Oct4 gene silencing on apoptosis in human colorectal cancer SW480 cell lines and its possible mechanism. Methods SW480480 cells at the late logarithmic phase were divided into 3 groups. (1) control group (Con): no virus transfection; (2) negative control group (NC): transfected with negative control viruses; (3) RNA interference group (RNAi): transfected with Oct4-shRNA lentiviral vector plasmids. In the above three groups, the Oct4 mRNA level was detected by real-time quantitative PCR, the protein levels of Oct4 and p-Akt were detected by Western blotting, and the proportion of Oct4+ and CD44+ cells and apoptosis of the tumor were analyzed by flow cytometry. Results Compared with those in the NC group, the Oct4 mRNA levels (1.00 vs 0.19±0.02), the Oct4 protein levels (0.032±0.004 vs 0.007±0.001), the p-Akt protein levels (0.11±0.03 vs 0.03±0.01), the proportion of Oct4+ cells (91.53% vs 10.70%) and the proportion of CD44+ cells (59.69% vs 23.58%) in the RNAi group significantly reduced, while cells apoptosis in the RNAi group significantly increased (43.2%±4.5% vs 12.1%±1.8%, P < 0.01). Conclusion Oct4 gene silencing could significantly reduce the proportion of Oct4+ and CD44+ cells, and obviously increase apoptosis in SW480 cells, which may be related to the PI3K/Akt pathway.

Colorectal cancer (CRC) is a common gastrointestinal malignancy worldwide and is a lethal and aggressive malignancy with a dismal prognosis. EphrinB2 is a membrane-bound ligand and has an intracellular domain that also possesses an intrinsic signaling capacity called 'reverse signaling'. In the present study, CRC cell lines were screened for high expression of ephrinB2. Small interfering RNA (siRNA) knockdown of ephrinB2 was performed in human SW480 CRC cells. The levels of expression of ephrinB2, VEGF, CD105 and matrix metalloproteinase 9 (MMP9) protein were measured by western blotting, and messenger RNA (mRNA) levels were measured using real-time PCR. Apoptosis and cell cycle distribution were determined using flow cytometry. Cell proliferation was measured by a methyl thiazole tetrazolium (MTT) test and a scratch healing experiment was used to measure the extent of cell migration. A Transwell assay was used to detect the extent of cell invasion. The results showed that RNA interference (RNAi) of ephrinB2 effectively silenced the ephrinB2 gene at both the mRNA and protein levels in SW480 cells and inhibited the proliferation, invasion, migration and angiogenesis and induced apoptosis in SW480 cells. These effects may be attributed to VEGF and MMP9 regulation.

Hepatic fibrosis is a major consequence of liver aggression. Finding novel ways for counteracting this damaging process, and for evaluating fibrosis with a non-invasive imaging approach, represent important therapeutic and diagnostic challenges. Hepatocyte growth factor (HGF) is an anti-fibrosis cell growth factor that induces apoptosis in activated hepatic stellate cells, reduces excessive collagen deposition, and stimulates hepatocyte regeneration. Thus, using HGF in gene therapy against liver fibrosis is an attractive approach. The aims of the present study were: (i) to explore the efficacy of treating liver fibrosis using HGF expression vector carried by a novel ultrasound microbubble delivery system; (ii) to explore the diagnostic interest of diffusion-weighted MRI (DWI-MRI) in evaluating liver fibrosis. We established a rat model of hepatic fibrosis. The rats were administered HGF linked to novel ultrasound micro-bubbles. Progression of hepatic fibrosis was evaluated by histopathology, hydroxyproline content, and DWI-MRI to determine the apparent diffusion coefficient (ADC). Our targeted gene therapy produced a significant anti-fibrosis effect, as shown by liver histology and significant reduction of hydroxyproline content. Moreover, using DWI-MRI, the b value (diffusion gradient factor) was equal to 300s/mm(2), and the ADC values significantly decreased as the severity of hepatic fibrosis increased. Using this methodology, F0-F2 could be distinguished from F3 and F4 (P0.01). This is the first in vivo report of using an ultrasound microbubble-cationic nano-liposome complex for gene delivery. The data indicate that, this approach is efficient to counteract the fibrosis process. DWI-MRI appears a promising imaging technique for evaluating liver fibrosis.

Cancer stem cells (CSCs) have been implicated in multidrug resistance, a phenomenon responsible for the failure of cancer chemotherapy. However, the underlying mechanisms are still unclear. In our study, we established two oxaliplatin-resistant colorectal cancer cell lines displaying some CSCs characteristics. Oct4 overexpression was observed in these two lines. We performed Oct4 knock down by lentiviral vector-mediated specific shRNA. Knockdown increased apoptosis, decreased CSCs marker expression and weakened tumorigenicity in drug-resistant cell lines. In conclusion, we show that these events can be at least in part attributed to the STAT3/Survivin pathway.