MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A.

BACKGROUND: Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission. AIM: To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance. METHODS: To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis. RESULTS: We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298's direct target. CONCLUSION: Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.

Knockdown of hCINAP sensitizes colorectal cancer cells to ionizing radiation.

Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure. Subsequent analysis revealed a notable increase in hCINAP expression in radiation-resistant CRC cells. To elucidate the functional role of hCINAP in radio-resistance, knockdown experiments were conducted. Remarkably, knockdown of hCINAP resulted in an elevation of reactive oxygen species (ROS) generation upon radiation treatment and subsequent activation of apoptosis mediated by mitochondria. These observations indicate that hCINAP depletion enhances the radiosensitivity of CRC cells. Conversely, when hCINAP was overexpressed, it was found to enhance the radio-resistance of CRC cells. This suggests that elevated hCINAP expression contributes to the development of radio-resistance. Further investigation revealed an interaction between hCINAP and ATPase family AAA domain containing 3A (ATAD3A). Importantly, ATAD3A was identified as an essential factor in hCINAP-mediated radio-resistance. These findings establish the involvement of hCINAP and its interaction with ATAD3A in the regulation of radio-resistance in CRC cells. Overall, the results of this study demonstrate that upregulating hCINAP expression may improve the survival of radiation-exposed CRC cells. Understanding the intricate molecular mechanisms underlying hCINAP function holds promise for potential strategies in targeted radiation therapy for CRC. These findings emphasize the importance of further research to gain a comprehensive understanding of hCINAP's precise molecular mechanisms and explore its potential as a therapeutic target in overcoming radio-resistance in CRC. By unraveling the complexities of hCINAP and its interactions, novel therapeutic approaches may be developed to enhance the efficacy of radiation therapy and improve outcomes for CRC patients.

Association between Three Therapeutic Strategies and Clinical Outcomes of 2009 FIGO Stage IB2/IIA2 Cervical Cancer.

Objective: The aim of this study was to compare clinical outcomes of three therapeutic strategies in patients with stage IB2/IIA2 cervical cancer. Methods: This is a retrospective cohort study. Patients diagnosed with stage IB2/IIA2 cervical cancer between April 2010 and December 2015 at First Affiliated Hospital of Guangxi Medical University were included and classed into three groups. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes included toxicity, hospitalization costs, clinical value, and length of stay. Results: 206 patients were included: 104 used primary surgical treatment (PST), 53 used neoadjuvant chemotherapy followed by radical surgery (NAC + RS), and 49 used concurrent chemoradiotherapy (CCRT). Fewer patients with NAC + RS had deep cervical stromal invasion than primary surgical treatment (PST) (P=0.024). 70.2% of PST and 77.4% in NAC + RS required postoperative radiotherapy or chemoradiotherapy (P=0.634). Median follow-up was 57 months and the 3-year OS and PFS in PST, NAC + RS, and CCRT group were 87.5%, 84.9%, 85.7% and 85.6%, 79.2%, 85.7% (P=0.856 and P=0.424, respectively). Three therapeutic strategies were not associated with OS and PFS. Hospitalization costs were significantly higher in NAC + RS compared to PST (P < 0.001) and CCRT (P < 0.001). Length of stay in NAC + RS was longer than PST (P < 0.001) and CCRT group (P=0.07). Conclusion: The results of this study tend to suggest that the three therapeutic strategies were equivalent treatment options for patients with 2009 FIGO stage IB2/IIA2 cervical cancer. However, prospective larger studies are needed to confirm this. In addition, we did find that concurrent chemoradiotherapy needed shorter treatment time and less cost.

Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle.

How mesenchymal stem cells (MSCs) promote tumor growth remains incompletely understood. Here, we show that mesenchymal stem-like cells (MSLCs) are commonly present in malignant pleural effusion or ascites of cancer patients, where they directly interact with tumor cells. Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. As a result, MSLCs exert tumor-promoting effects by enhancing the proliferation and colony formation of tumor-repopulating cells. The underlying molecular basis involves MSLC release of glutamine to tumorigenic cells. Inhibition of glutamine uptake impedes MSC-mediated tumor-promoting effects. More intriguingly, MSLCs take up tumor cell-released ammonium that, in turn, favors MSLC growth. Thus, glutamine and ammonium form a vicious cycle between MSLCs and tumorigenic cells. These findings suggest a potential clinical application by targeting MSLCs in patients with malignant pleural effusions or ascites.