5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I / 医学前沿

tRNA-derived small RNAs (tsRNAs) are novel non-coding RNAs that are involved in the occurrence and progression of diverse diseases. However, their exact presence and function in hepatocellular carcinoma (HCC) remain unclear. Here, differentially expressed tsRNAs in HCC were profiled. A novel tsRNA, tRNAGln-TTG derived 5'-tiRNA-Gln, is significantly downregulated, and its expression level is correlated with progression in patients. In HCC cells, 5'-tiRNA-Gln overexpression impaired the proliferation, migration, and invasion in vitro and in vivo, while 5'-tiRNA-Gln knockdown yielded opposite results. 5'-tiRNA-Gln exerted its function by binding eukaryotic initiation factor 4A-I (EIF4A1), which unwinds complex RNA secondary structures during translation initiation, causing the partial inhibition of translation. The suppressed downregulated proteins include ARAF, MEK1/2 and STAT3, causing the impaired signaling pathway related to HCC progression. Furthermore, based on the construction of a mutant 5'-tiRNA-Gln, the sequence of forming intramolecular G-quadruplex structure is crucial for 5'-tiRNA-Gln to strongly bind EIF4A1 and repress translation. Clinically, 5'-tiRNA-Gln expression level is negatively correlated with ARAF, MEK1/2, and STAT3 in HCC tissues. Collectively, these findings reveal that 5'-tiRJNA-Gln interacts with EIF4A1 to reduce related mRNA binding through the intramolecular G-quadruplex structure, and this process partially inhibits translation and HCC progression.

Construction and application of a perioperative management program of breast reconstruction with deep inferior epigastric perforator flap in patients with breast cancer / 中华护理杂志

Objective To construct a perioperative management program for breast reconstruction with deep inferior epigastric perforator flap with breast cancer,and to provide references for clinical practice.Methods The databases at home and abroad were searched to obtain the relevant literature,and the perioperative management program of breast reconstruction with inferior epigastric artery perforator flap for breast cancer was preliminarily constructed.3 rounds of expert inquiries were conducted by Delphi method from October 2022 to January 2023 to determine the final content of the program.14 patients who received breast reconstruction with deep inferior epigastric perforator flap in a tertiary hospital in Zhejiang Province from January to May in 2023 were selected as application subjects to implement the modified program and evaluate the clinical effect.Results A total of 15 experts completed 3 rounds of consultation.In the third round of consultation,the Kendall's concordance coefficient of the importance of the first-level indicators was 0.347(P<0.05);the Kendall's concordance coefficients of the importance of the second and third-level indicators were 0.388 and 0.200(P<0.001);the coefficient of variation of each indicator was 0～0.224.The final program included 3 first-level indicators,18 second-level indicators and 67 third-level indicators.The incidence of flap complications in 14 patients decreased by 11.9%.Conclusion The perioperative management program of breast reconstruction with deep inferior epigastric perforator flap for breast cancer is preliminarily applied in clinical practice,which is scientific,reliable and practical,and it can provide references for clinical nursing.

Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. @*Materials and Methods@#Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. @*Results@#CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. @*Conclusion@#CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.