Yantian Fang

MiR-301a Promotes Colorectal Cancer Cell Growth and Invasion by Directly Targeting SOCS6

Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC.

miRNA expression profile of colon cancer stem cells compared to non-stem cells using the SW1116 cell line.

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Recent studies revealed that there is a relationship between CRC occurrence and microRNA (miRNA) function. Stem cells are a type of cells that have the ability to self-renew and to proliferate extensively while maintaining the undifferentiated state. Cancer stem cells (CSCs) are closely linked to tumor recurrence and metastasis. To this end, we evaluated the miRNA expression differences between colon CSCs and non-stem cells using the SW1116 cell line, to determine the relationship between tumor stem cells and tumor biological behavior. We isolated populations of colon CSCs with the CD133+/CD44+ and CD133-/CD44- surface phenotype from a human SW1116 colon adenocarcinoma cell line using flow cytometry. The expression of miRNA and mRNA of both sets of cells was examined with miRNA and mRNA arrays. Bioinformatic methods were used to analyze microarray results. We completed gene ontology analysis, pathway analysis, miRNA target gene prediction with databases. We identified a colon stem cell miRNA expression profile comprising 31 upregulated and 31 downregulated miRNAs, such as miR29a, miR29b, miR449b and miR4524. Some of these differentially expressed miRNAs may be involved in the regulation of stem cell differentiation. Gene ontology and pathway analyses showed that the differences are closely related to the function of the cell cycle, cell differentiation, signaling pathway, cytoskeletal proteins and cell-matrix adhesion in colon cancer stem cells. We found that miRNAs play an important role in regulating the expression of colon CSC characteristics. By regulating the expression of CSC signaling pathways, cytoskeleton and membrane proteins, miRNAs give tumor stem cells the macrobiological behavior of recurrence and metastasis. This study provides a new perspective on CRC metastasis and recurrence.

Prognostic factors associated with locally recurrent rectal cancer following primary surgery (Review)

Locally recurrent rectal cancer (LRRC) is defined as an intrapelvic recurrence following a primary rectal cancer resection, with or without distal metastasis. The treatment of LRRC remains a clinical challenge. LRRC has been regarded as an incurable disease state leading to a poor quality of life and a limited survival time. However, curative reoperations have proved beneficial for treating LRRC. A complete resection of recurrent tumors (R0 resection) allows the treatment to be curative rather than palliative, which is a milestone in medicine. In LRRC cases, the difficulty of achieving an R0 resection is associated with the post-operative prognosis and is affected by several clinical factors, including the staging of the local recurrence (LR), accompanying symptoms, patterns of tumors and combined therapy. The risk factors following primary surgery that lead to an increased rate of LR are summarized in this study, including the surgical, pathological and therapeutic factors.

Epithelial-mesenchymal transition‑associated microRNAs in colorectal cancer and drug-targeted therapies (Review)

Colorectal cancer (CRC) is one of the most common malignancies, and the third leading cause of cancer‑associated mortality worldwide. Therefore, the identification of effective targets at the early stages of cancer invasion and metastasis, and new tumor markers for early diagnosis and individualized treatment is imperative for CRC. Epithelial‑mesenchymal transition (EMT) refers to the phenomenon of the transformation of epithelial cells to mesenchymal cells in specific physiological and/or pathological circumstances. Evidence suggests that EMT plays an important role in in situ infiltration and distant metastasis of many types of cancer, including CRC. Recent findings showed that microRNA expression is important in regulating the EMT process. This review aimed to summarize EMT-associated specific miRNA molecules in CRC, with particular emphasis on clinical targets for effective treatment of this lethal disease.

MiR‐622 inhibited colorectal cancer occurrence and metastasis by suppressing K‐Ras

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with many oncogenes and anti‐oncogenes involved. MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that can adjust downstream targets. Accumulating evidence has revealed that microRNAs govern the occurrence and development of cancer. Here, we studied the role of miR‐622 in CRC and clarified the underlying mechanism. We detected that miR‐622 was down‐regulated in colorectal tumor tissues and cell lines and that miR‐622 was lower in metastatic CRC tissues compared with that in non‐metastatic specimens. Furthermore, we confirmed that miR‐622 inhibited tumor proliferation and migration in vitro. Through dual‐luciferase reporter assay, we found kirsten rat sarcoma (K‐Ras) gene was the direct target of miR‐622. More importantly, K‐Ras overexpression can rescue the inhibitory effect of miR‐622 on CRC development. All these data were validated in colon xenograft tumor model. MiR‐622‐K‐Ras signal pathway was a potentially new direction in the development of screening target and therapeutic treatments for CRC.

Mesenteric lymphatic hygroma in adults: A case report with a review of the literature.

Mesenteric lymphatic hygroma is a benign tumor of lymphatic origin that is rarely observed in adult patients. Congenital and developed non-specific symptoms, including abdominal distension, pain and ileus, develop at an early age in patients. This type of disease is usually reported by pediatric doctors, as referred to in the literature. The current study presents the case of a 23-year-old male in whom a polycystic mass in the mesentery was identified by computed tomography. The size of the tumor was measured to be 30×20×15 cm during surgery. The mass was excised completely with preservation of the intestine, duodenum, pancreas and other neighboring organs. Histopathological examination confirmed the diagnosis of lymphatic hygroma. The post-operative recovery was uneventful, with the exception of chylous leakage for one week, which was relieved spontaneously. In addition, the present study presents a review of the previous literature concerning mesenteric lymphatic hygroma.

Perioperative mortality and morbidity prediction using POSSUM, P-POSSUM and APACHE II in Chinese gastric cancer patients: surgical method is a key independent factor affecting prognosis.

IntroductionGastric cancer is the fourth most common cancer worldwide. Predicting morbidity and mortality is important in deciding timing of surgery and type of surgery offered. APACHE II, POSSUM, and P-POSSUM are the most reliable scoring methods in use today. This is the first paper to evaluate the utility of all three scoring systems in China.MethodsWe collected data on 851 patients (583 male and 268 female) who underwent surgery between 1991 and 2011. Physiological and pathological data was entered in spreadsheet format and analyzed using STATA version 11.0 to generate ROC curves for each scoring system.ResultsIn predicting mortality, P-POSSUM and POSSUM were most effective and APACHE II was ineffective. POSSUM predicted a higher morbidity risk than was actually encountered. Age and type of operation were found to be independent risk factors for mortality.DiscussionThe utility of the APACHE II score in gastric cancer patients is limited. APACHE II is suitable for considering group versus individual effect. The POSSUM score is useful in general surgery, but needs improvement. We found the P-POSSUM score to be superior for morbidity and mortality prediction. P-POSSUM is useful for both the general population and for a specific cohort. The type of surgery is a key decision point for surgeons, and independently affects prognosis. Based upon these findings and clinical scoring systems, clinicians can develop individualized treatment algorithms.