Retraction Notice to: lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.009.].

lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

Colorectal cancer (CRC) is a frequently occurring lethal disorder with heterogeneous outcomes and drug responses. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis. Hence, the aim of this study was to investigate the role of lncRNA growth arrest-specific 5 (GAS5) in CRC cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN)-signaling pathway. HCT116 and SW480 cells were collected and treated with small interfering (si)-lncRNA GAS5, overexpressing (oe)-lncRNA GAS5, miR-222-3p mimic, miR-222-3p inhibitor, or si-lncRNA GAS5 + miR-222-3p mimic. The miR-222-3p level and mRNA and protein levels of GAS5, Beclin1, light-chain 3B (LC3B), PTEN, and Akt were detected. Besides, cell migration, invasion, and apoptosis as well as acidic vesicular organelles (AVOs) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that the downregulation of lncRNA GAS5 decreased the expressions of Beclin1, LC3B, and PTEN. When treated with oe-lncRNA GAS5 or miR-222-3p inhibitor, HCT116 and SW480 cells exhibited suppressed invasion and migration abilities and increased apoptotic cells and autophagosome and AVO activities. Moreover, overexpression of GAS5 inhibited the tumorigenesis of CRC cells in vivo. Taken together, lncRNA GAS5 upregulated the expression of PTEN by functioning as a competing endogenous RNA (ceRNA) of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.

MiR-590-3p promotes proliferation and metastasis of colorectal cancer via Hippo pathway.

Studies reported that miR-590-3p was involved in human cancer progression. However, its roles of oncogene or anti-oncogene in malignancies still remain elusive. This study was aimed to investigate the effect of miR-590-3p on the cell proliferation and metastasis via Hippo pathway in colorectal cancer (CRC). In our study, miR-590-3p was demonstrated highly expressed in CRC tissues, compared with adjacent normal tissues (P<0.05). In addition, miR-590-3p was positively associated with TNM stage and distant metastasis. Survival analysis showed that high miR-590-3p was related with poor overall survival rate. Then, over-expressed miR-590-3p was demonstrated to promote proliferation, invasion and migration of colon caner cells. What's more, MST1, LATS1 and SAV1 mRNA were showed lowly expressed and YAP1 expression in mRNA and protein levels were highly expressed in CRC tissues, compared with adjacent normal tissues (all P<0.05). miR-590-3p expression was negatively associated with LATS1 and SAV1 mRNA respectively and positively related with YAP1 mRNA in CRC tissues, meanwhile, there was no relationship between miR-590-3p and MST1 mRNA. Furthermore, over-expressing miR-590-3p inhibited expressions of LATS1 and SAV1, promoted YAP1 expression and didn't effect MST1 expression in colon cancer cells. And luciferase assay showed that miR-590-3p over-expression inhibited the luciferase activity of LATS1 and SAV1 3'UTR, meanwhile it had no effect on the mutated form of these two plasmids. Taken together, these data suggest that highly-expressed miR-590-3p promotes biological effect of proliferation and metastasis via targeting Hippo pathway, and predicts worse clinical outcomes of CRC patients.

The Surgical Technique of Laparoscopic Lymph Node Dissection Around the Inferior Mesenteric Artery with Preservation of Superior Rectal Artery and Vein for Treatment of the Sigmoid and Rectal Cancer.

BACKGROUND: The inferior mesenteric artery (IMA) is usually divided during the resection of sigmoid colon and rectal cancers. However, this sometimes results in a vein (SRA\V) insufficient blood supply to the anastomosis, leading to anastomotic leakage. We summarized the experience of laparoscopy surgery approach to perform the D3 lymph node dissection with preserving the superior rectal artery and vein. METHODS: Our method involves peeling off the vascular sheath from the inferior mesenteric vessel to the superior rectal vessel and dissection of the lymph node around the IMA together with the sheath. The feasibility outcomes of the technique were evaluated in 36 cases of laparoscopic resection of sigmoid and rectal cancer. RESULTS: Our method involves peeling off the vascular sheath from the inferior mesenteric vessel to the superior rectal vessel and dissection of the lymph node around the IMA together with the sheath. The feasibility of the technique was evaluated in 36 consecutive cases of laparoscopic resection of sigmoid and rectal cancer. Patients with sigmoid or rectal cancer underwent operation via the present laparoscopic approach. No serious complications related to the approach were encountered. The number of cleared lymph nodes was 17 (range 10-35). The operation time was 200 (range 160-300) minutes. The blood loss was 50 (range 20-100) mL. Anastomotic leakage never occurred in these patients without preoperative chemoradiation therapy, the patients had quick convalescence, as evaluated by the recovery of flatus passage (2.8 ± 1.5 days), postoperative hospitalization (10.8 ± 4.6 days), degree of postoperative pain for 48 hours (2.5 ± 0.5, visual analog scale), duration of postoperative ambulation (1.5 ± 0.5 days), and drainage tube removal time (1.0 ± 0.4 days). CONCLUSION: Our method allows equivalent laparoscopic lymph node dissection to the preservation of the SRA\V technique without excessive operative time, complications, or bleeding. It seems to be a promising and feasible technique for these patients with sigmoid and rectal cancer.

[Effects of increased body mass index upon laparoscopic radical rectal surgery and its clinical efficacy].

OBJECTIVE: To assess the feasibility, the safety and short-term outcomes of laparoscopic radical rectal surgery for rectal cancer patients with increased body mass index (BMI) . METHODS: Retrospectively data reviews were conducted for 405 consecutive patients undergoing laparoscopic surgery for rectal cancer from June 2008 to June 2012. They were classified as normal-weight (NW, BMI 18.6-22.9 kg/m(2), n = 165), overweight (OW, BMI 23.0-24.9 kg/m(2), n = 125), and obese (OB, BMI ≥ 25.0 kg/m(2), n = 115)groups according to the categories as proposed by 2007 Chinese Obesity Surgery Treatment Guidelines. The differences of oncologic, intraoperative and postoperative status, postoperative complications, number of resected lymph nodes and short-term survival rates were compared among three groups. The data were analyzed by χ(2) or Fisher exact test. The Mann-Whitney U test or analysis of variance (one-way ANOVA) was used for parametric comparisons. The survival curve was drawn by Kaplan Meier method and the survivals of 3 groups were by the Log-rank test. RESULTS: The comorbidity of patients in the NW and OW groups were less than that in the OB group(27.9% (46/165) and 30.4% (38/125) vs 47.0% (54/115), χ(2) = 12.066, P < 0.05). No significant difference existed among the groups in terms of conversion rate (9.1% (15/165), 10.4% (13/125) and 12.2% (14/115)), the rate of postoperative complications (20.6% (34/165), 21.6% (27/125) and 24.3% (28/115) ), intraoperative volume of blood loss ((105 ± 30), (110 ± 25) and (115 ± 45) ml), first flatus( (2.8 ± 1.2), (2.9 ± 1.1) and (3.1 ± 1.4) d), postoperative hospital stays ((13.7 ± 5.5), (14.3 ± 7.5) and (14.1 ± 8.5) d, all P > 0.05), and the mean number of retrieved lymph nodes(P > 0.05). While the operation duration in the OB group were longer than that in the NW and OW groups ((250 ± 35) vs (205 ± 20) and (210 ± 30) min, F = 7.216, P < 0.05) . And 368 patients (90.9%) were followed up for a median of 24 months(2-48 months). As for survival curves, no significant difference existed among three groups (P > 0.05). CONCLUSIONS: It is both safe and feasible for obese patients with increased BMI to undergo laparoscopic radical rectal cancer. And there is no effect upon immediate survival.

Significance of HPV infection and genic mutation of APC and K-ras in patients with rectal cancer.

BACKGROUND: Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has been investigated but not clarified. The objective of our study was to investigate these parameters in patients with rectal cancer to analyze correlations with biological behaviour, to determine relationships among the three, and also to demonstrate survival prognosis effects. METHODS: From December 2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. The control group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. All results were analyzed in relation to clinical pathological material, using chi-square and correlation analysis via SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysis using Kaplan-Meier and Log-rank tests. RESULTS: 55 out of 75 cases demonstrated gene HPV L1 while it was not detected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC genic mutation was correlated with gender( P<0.05), but not age, histological type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of rectal cancer with HPV infection, there were 31 cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with no significant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genic mutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a little shorter than in cases without HPV infection. CONCLUSIONS: Our results suggest that HPV infection might be an important factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutation of APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects on medium-term or early stage patients with rectal cancer.

[Clinical characteristics and prognostic analysis of 45 patients with high-risk gastrointestinal stromal tumors].

OBJECTIVE: To investigate the clinical characteristics and prognosis factors of primary resectable high-risk gastrointestinal stromal tumors (GIST). METHODS: The clinicopathological and follow-up data of 45 patients with primary resectable high-risk gastrointestinal stromal tumors between January 2002 and November 2010 were retrospectively reviewed. RESULTS: Forty-five patients included 18 males and 27 females with a median age of 48 years (range, 28-77 years). Of 45 tumors, 19 (42.2%) located in the stomach, 9 (20.0%) in the small intestine, 7 (15.6%) in the rectum, 4 (8.9%) in the mesentery, and 6 (13.3%) in the retroperitoneum. All the patients received surgical resection and 35 (77.8%) underwent complete resection, 10 (22.2%) underwent resection of ruptured tumors (before or during operation), 33 (73.3%) underwent R0 resection, 5 (11.1%) underwent R1 resection, and 7 (15.6%) underwent R2 resection. All the patients received targeted therapy of imatinib after surgery. The median duration of imatinib was 24 (10-99) months. The main side effect was noticed in all the patients, mainly including edema in 39 (86.7%) patients and leukopenia in 27 (60.0%) patients. The relapse rate was 37.8% (17/45). The 1-, 3-, and 5-year survival rates were 100%, 86.7% and 74.4%, respectively. Univariate and multivariate analysis revealed that the degree of resection was independently associated with the prognosis of high-risk GIST patients. CONCLUSIONS: Surgery is effective treatment for the GIST. Efforts to obtain R0 resection are important to improve the efficacy of primary resectable high-risk GIST.

Expression of smoothened protein in colon cancer and its prognostic value for postoperative liver metastasis.

UNLABELLED: BACKGROUDS: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. METHODS: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. RESULTS: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression (48.7 ± 8.02 months vs 28.0 ± 6.86 months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). CONCLUSIONS: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.