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Objective To investigate the effect of tRNA fragment differentially expressed between high and low malignant bladder urothelial carcinoma (BUC) cells induced by heat injury on the proliferation and invasion of BUC cells. Methods High-grade BUC cell line T24 and low-grade BUC cell line 5637 were inflicted to heat injury. Then transfer RNA stress-induced fragments (tRFs) in these cells were sequenced before and after injury, and the tRFs whose expression decreased in T24 cells while increased in 5637 cells after heat injury were screened out, and further verified in clinical specimen by RT-PCR. The single-chain mimic and antisense strand (inhibitor) of this target tRF were constructed and transfected into heat injured T24 and 5637 cells respectively, and the cells were assigned into heat injury, vector control, mimic and inhibitor groups. Finally, CCK-8 assay, flow cytometry and Transwell test were conducted respectively to detect the regulatory effect of this tRF on the proliferation, apoptosis, migration and invasion of BUC cells. Results The originally selected tRFs were identified as tRF-chrM.Ser-GCT and tRF-Ile-AAT-1 through sequencing and RT-PCR in cell lines. However, when comparing the specimens from the second surgery of transurethral resection of bladder tumor (TURBT) with those from the first one, the results discovered that only tRF-Ile-AAT-1 levels were increased in low-grade BUC patients (1.61±0.16 times, P < 0.01) while decreased in high-grade BUC patients (0.75±0.14 times, P < 0.05). In the T24 cells experiments, when compared with the T24Heat group, the proliferation of BUC cells in the T24Heat+Mimic group was inhibited (P < 0.05), the apoptotic rate was significantly improved (5.88±1.01 times, P < 0.01), and the number of migrated and invaded cells were both greatly diminished (0.40±0.05 times, P < 0.01; 0.23±0.04 times, P < 0.01). Moreover, the proliferation of BUC cells in the 5637Heat+ Inhibitor group was enhanced (P < 0.05), the apoptotic rate was declined (0.11±0.02 times, P < 0.01), and the number of migrated cells as well as invaded cells were both elevated (1.81±0.29 times, P < 0.01; 2.70±0.15 times, P < 0.01), as compared with the 5637Heat group. Conclusion tRNA fragment tRF-Ile-AAT-1 induced by heat injury can inhibit the proliferation and invasion in BUC cells

Background: Breast cancer is a prevalent disease that has a dismal prognosis for patients and a bad outlook for treatments. Ubiquitination is a reversible biological process that regulates protein production and degradation, as well as plays a vital role in protein transport, localization, and biological activity., Methods: We obtained the breast cancer patient sample data and used a machine learning technique to create a novel index called Deubiquitinating enzyme related index (DUBRI) by gathering genes associated to deubiquitinating enzymes. Based on DUBRI, we systematically analyze patients' prognosis, clinical characteristics, tumor immune microenvironment, chemotherapy response and immunotherapy response. Finally, the function of OTUB2 was explored in breast cancer cells., Results: DUBRI, which consists of five deubiquitinating enzyme genes (OTUB2, USP41, MINDY2, YOD1, and PSMD7), is a reliable predictor of survival in breast cancer patients. We found that the high DUBRI group presented higher levels of immune cell infiltration. We performed molecular docking prediction of core target proteins in deubiquitinating enzymes. In vitro experiments verified that knockdown of OTUB2 could inhibit the proliferation and migration of breast cancer., Conclusions: The DUBRI discovered in this research may effectively evaluate the outlook of breast cancer patients and identify groups of patients who would gain advantages from immunotherapy, offering vital knowledge for the future targeted treatment of breast cancer patients.

HOXA transcript at the distal tip (HOTTIP), a lncRNA, induces cell proliferation and cancer progression. However, the expression and function of HOTTIP in renal cell carcinoma (RCC) were rarely reported. The role of the HOTTIP in RCC was explored in this study. HOTTIP expresses higher in RCC tissues than in normal tissues and indicates poor prognosis based on the TCGA database. The over- and low-expression HOTTIP cell line was established in this research to assess the oncogenic function of HOTTIP in RCC progression. Mechanistic analyses revealed that HOTTIP functioned as a competing endogenous RNA (ceRNA) for miR-506. RIP experiment and luciferase assay were performed to explore the mechanisms of the sponge between HOTTIP and miR-506. HOTTIP down-regulation attenuated cell proliferation, migration, and invasion, which could be rescued by miR-506 down-regulation. On the whole, this study revealed that the HOTTIP/miR-506 axis has a dominant impact on RCC progression and potentially provides a novel strategy for RCC diagnosis and therapy.