Background/Aims. TRPV1 is a nonselective Ca2+ channel which has recently been observed in many cancers, while its effect on cell proliferation, apoptosis, metabolism, and cancer development in colorectal cancer (CRC) is still unclear. In this study, we hypothesized that TRPV1 is a tumor suppressor in CRC development as well as the underlying mechanism. Methods. Immunohistochemistry assay was applied to detect the expression of TRPV1 protein in CRC tissues. HCT116 cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. Cellular Ca2+ concentration was measured by Fluo-4/AM-based flow cytometer. Apoptosis-related proteins were measured by Western blotting. Results. In this study, we found that TRPV1 expression was significantly decreased in CRC tissues, compared with CRC-adjacent tissues and normal tissues, respectively. Then, we found that the TRVP1 agonist capsaicin treatment inhibited CRC growth and induced apoptosis by activating P53. Subsequent mechanistic study revealed that the TRPV1 induced cytosolic Ca2+ influx to regulate cell apoptosis and p53 activation through calcineurin. Conclusions. This study suggests that TRPV1 served as a tumor suppressor in CRC and contributed to the development of novel therapy of CRC.

LIN28B is involved in “stemness” and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer.

MicroRNA (miR)-370 functions as a tumor suppressor or promoter in several cancers. However, the expression and biological role of miR-370 in colon cancer remains undefined. In the present study, miR-370 expression in both normal and malignant colon tissues was quantified by quantitative polymerase chain reaction. An in vitro cell viability and apoptosis assay and an in vitro xenograft tumor model were employed to investigate the role of miR-370 on colon cancer growth. Furthermore, the potential direct target of miR-370 was identified using a luciferase assay. Our results demonstrate that down-regulation of miR-370 expression occurs in malignant tissues and miR-370 expression is inversely correlated with tumor grade. Moreover, we determined that miR-370 functions as a tumor suppressor in colon cancer by inhibiting cell proliferation and promoting cell apoptosis. In addition, overexpression of miR-370 impairs xenograft tumor growth in nude mice. Mechanistically, mouse double minute 4 (MDM4) was demonstrated to be a potential direct target of miR-370, inducing apoptosis in colon cancer. Collectively, these findings suggest that upregulation of miR-370 may impair colon tumor growth by directly targeting MDM4. These findings provide a new direction for the diagnosis and treatment of colon cancer.

PurposeTo determine whether gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict presence of lymphovascular invasion and T-stages.ResultsGross tumor volume increased with the lymphovascular invasion (r = 0.426, P < 0.0001) and T stage (r = 0.656, P < 0.0001). Univariate analysis showed gross tumor volume could predict lymphovascular invasion (P < 0.0001). Multivariate analyses indicated gross tumor volume as an independent risk factor of lymphovascular invasion (P = 0.026, odds ratio = 2.284). The Mann-Whitney U test showed gross tumor volume could distinguish T2 from T3, T1 from T2–T4a, T1–T2 from T3–T4a and T1–T3 from T4a (P = 0.000). In the development cohort, gross tumor volume could predict lymphovascular invasion (cutoff, 15.92 cm3; AUC, 0.760), and distinguish T2 from T3 (cutoff, 10.09 cm3; AUC, 0.828), T1 from T2-T4a (cutoff, 8.20 cm3; AUC, 0.860), T1-T2 from T3-T4a (cutoff, 15.88 cm3; AUC, 0.883), and T1-T3 from T4a (cutoff, 21.53 cm3; AUC, 0.834). In validation cohort, gross tumor volume could predict presence of lymphovascular invasion (AUC, 0.742), and distinguish T2 from T3 (AUC, 0.861), T1 from T2-T4a (AUC, 0.859), T1–T2 from T3–T4a (AUC, 0.875), and T1–T3 from T4a (AUC, 0.773).Materials and Methods360 consecutive patients with gastric adenocarcinoma were retrospectively identified. Gross tumor volume was evaluated on multidetector computed tomography images. Statistical analysis was performed to determine whether gross tumor volume could predict presence of lymphovascular invasion and T-stages. Cutoffs of gross tumor volume were first investigated in 212 patients and then validated in an independent 148 patients using area under the receiver operating characteristic curve (AUC) for predicting lymphovascular invasion and T-stages.ConclusionsGross tumor volume of resectable gastric adenocarcinoma at multidetector computed tomography demonstrated capability in predicting lymphovascular invasion and distinguishing T-stages.

MicroRNA-21-3p (miR-21-3p), the passenger strand of pre-mir-21, has been found to be high-expressing in various cancers and to be associated with tumour malignancy, which is proposed as a novel focus in malignant tumours. Colorectal cancer (CRC), currently known as one of the most prevalent malignancy, is a leading cause of cancer death. This study aimed to investigate the key role of miR-21-3p in CRC by inhibiting its expression using transfection with miR-21-3p inhibitors into human CRC HCT116 cells. Results showed that the expression of miR-21-3p was higher than other CRC cells used in the study including Lovo, HT29, Colo320 and SW480 cells, inhibition of which suppressed the proliferation and induced cell cycle arrest in HCT116 cells. Besides, transfection with miR-21-3p inhibitors also attenuated cell migration and invasion, and induced apoptosis as well. Moreover, luciferase assay confirmed RBPMS as a direct target of miR-21-3p in HCT116 cells. Further, miR-21-3p inhibitors increased the nuclear accumulation of Smad4 and reduced phosphorylation of ERK. Interestingly, we found that silence of RBPMS using RNA interference (siRNA) not only elevated the cell viability but also increased the phosphorylation of ERK and reversed the nuclear accumulation of Smad4 induced by miR-21-3p inhibitors in HCT116 cells. Data suggest that inhibition of miR-21-3p suppresses cell proliferation, invasion as well as migration and induces apoptosis by directly targeting RBPMS through Smad4/ERK signalling pathway in HCT116 cells. Our study demonstrates miR-21-3p as a potent target for suppressing tumour progression of CRC which may have implications in CRC therapy in the future.