Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed and the second cancer-related death worldwide, leading to more than 0.9 million deaths every year. Unfortunately, this disease is changing rapidly to a younger age, and in a more advanced stage when diagnosed. The DEAD-box RNA helicase proteins are the largest family of RNA helicases so far. They regulate almost every aspect of RNA physiological processes, including RNA transcription, editing, splicing and transport. Aberrant expression and critical roles of the DEAD-box RNA helicase proteins have been found in CRC. In this review, we first summarize the protein structure, cellular distribution, and diverse biological functions of DEAD-box RNA helicases. Then, we discuss the distinct roles of DEAD-box RNA helicase family in CRC and describe the cellular mechanism of actions based on recent studies, with an aim to provide future strategies for the treatment of CRC.

Investigating the WNT/TCF pathway and the value of DCE-MRI in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy for locally advanced rectal cancer.

The purpose of this research was to Detach the DCE-MRI value in predicting and evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy in middle and low locally advanced rectal cancer (READ). For this purpose, 40 patients with READ were examined by DCE-MRI and DWI before CRT treatment and 4 weeks after CRT treatment, and examined by Avanto1.5T magnetic resonance imaging scanner. According to the comparison of the postoperative pathological T stage and pre-nCRT T stage, the patients with decreased stage were defined as the T-descending group, and those with unchanged or elevated staging were defined as the T-undescending group. The ROC curve was used to evaluate the value of ADC value and Ktrans value to predict the early curative effect of neoadjuvant radiation therapy and chemotherapy for READ. Results showed that The ADC values of the two groups after nCRT were higher than those before nCRT (P<0.05). Compared with the pre-nCRT T-decline group and T-non-decline group, the Ktrans value of the pre-T-decline group was higher than that of the T-non-decline group (P<0.05), and the Ktrans value of both groups after the nCRT was higher than that before nCRT (P<0.05). The difference and the rate of ADC in the T-depression group were higher than in the T-undescending group (P<0.05). Taking the change rate of the ADC value 0.17 as the optimal threshold, the sensitivity and specificity of predicting the T-descending stage of patients with READ after neoadjuvant radiotherapy and chemotherapy were 72.69% and 75.84%, respectively (95%CI:0.608-0.954); taking the pre-nCRTKtrans value 1.18/min as the optimal threshold, the sensitivity and specificity to predict the T-descending stage of READ patients after neoadjuvant radiation therapy and chemotherapy was 78.65% and 80.47%, respectively (95%CI:0.637-0.971). There was no significant difference between the change rate of ADC value and the Ktrans value before nCRT in predicting the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. In conclusion, ADC value and Ktrans value can reflect the tissue structure changes of READ after neoadjuvant chemotherapy. It can be seen that the change rate of ADC value and pre-nCRTKtrans value can predict the early efficacy of neoadjuvant radiotherapy and chemotherapy for READ. The results showed that Axin2 and ß-catenin factors along with other factors such as APC and CKI proteins are effective at the molecular level along with other factors in the WNT/TCF signaling pathway. These agents start their activity in the cytoplasm and exert their final effect on the genes in the nucleus.

Berberine induces SOCS1 pathway to reprogram the M1 polarization of macrophages via miR-155-5p in colitis-associated colorectal cancer.

Berberine is approved for the treatment of intestinal infections and diarrhea and has been shown to have anti-inflammatory and anti-tumor effects in pathological intestinal tissues. However, it is unclear whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CAC). In this study, we found that berberine effectively inhibited tumorigenesis and protected against colon shortening in CAC mouse model. Immunohistochemistry results showed a reduction in the number of macrophage infiltrations in the colon following berberine treatment. Further analysis revealed that most of the infiltrated macrophages were pro-inflammatory M1 type, which berberine effectively limited. However, in another CRC model without chronic colitis, berberine had no significant effect on tumor number or colon length. In vitro studies demonstrated that berberine treatment significantly reduced the percentage of M1 type and levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Additionally, miR-155-5p level was down-regulated, and suppressor of cytokine signaling 1 (SOCS1) expression was up-regulated in berberine-treated cells. Notably, the miR-155-5p inhibitor attenuated the regulatory effects of berberine on SOCS1 signaling and macrophage polarization. Altogether, our findings suggest that the inhibitory effect of berberine on CAC development is dependent on its anti-inflammatory activity. Moreover, miR-155-5p may be involved in the pathogenesis of CAC by regulating M1 macrophage polarization, and berberine could be a promising protective agent against miR-155-5p-mediated CAC. This study provides new insights into pharmacologic mechanisms of berberine and supports the possibility that other anti-miR-155-5p drugs may be beneficial in the treatment of CAC.

The employment of vaccinia virus for colorectal cancer treatment: A review of preclinical and clinical studies.

Colorectal cancer (CRC) is one of the leading malignancies that causes death worldwide. Cancer vaccines and oncolytic immunotherapy bring new hope for patients with advanced CRC. The capability of vaccinia virus (VV) in carrying foreign genes as antigens or immunostimulatory factors has been demonstrated in animal models. VV of Wyeth, Western Reserve, Lister, Tian Tan, and Copenhagen strains have been engineered for the induction of antitumor response in multiple cancers. This paper summarized the preclinical and clinical application and development of VV serving as cancer vaccines and oncolytic vectors in CRC treatment. Additionally, the remaining challenges and future direction are also discussed.