Yufeng Li

Tectochrysin inhibits colorectal cancer progression by targeting ERBB4 signaling.

The lactylation modification has been implicated in several cancer types; however, the role of lactylation modification-related genes in esophageal carcinoma (EC) remains underexplored. Utilizing a set of 16 lactylation modification-related genes, cohorts of patients with EC were stratified into two distinct clusters, characterized by significant disparities in both survival outcomes and the immune microenvironment. An extensive bioinformatics analysis unveiled 382 differentially expressed genes (DEGs) between these two clusters. A subsequent univariate Cox regression analysis identified 24 DEGs specifically associated with lactylation, forming the basis of a constructed lactylation-related score. The resultant lactylation-related score exhibited notable predictive efficacy for survival and other clinicopathological traits, which was validated through calibration curves, Kaplan–Meier survival curves and the Wilcoxon test. Moreover, the lactylation-related score displayed a close correlation with immune cell infiltration in EC. Notable differential expressions of immune checkpoints and regulators were observed between groups stratified by low and high lactylation scores, with the latter exhibiting a more favorable response to anti-PD-1/PD-L1 therapy. Furthermore, the expression profile of U2 snRNP associated SURP domain containing (U2SURP), a constituent of the lactylation-related score, underwent both ex vivo and in vitro validation. The expression of U2SURP was significantly associated with lactylation levels, histological grade and tumor stage. Notably, knockdown of U2SURP expression inhibited the lactylation levels, immune genes IL-1A and IL-1B, proliferation, migration and invasion of EC cells. In conclusion, the lactylation-related score developed in the present study showed promise in predicting the prognosis and immunotherapeutic responses among patients with EC. Moreover, the identification of U2SUPR as a novel oncogene in EC suggests its potential as a prospective therapeutic target for EC treatment.

Background: Long noncoding RNAs played critical roles in glioblastoma development. Objectives: This study aimed to examine the impacts of lncRNA DLK1-35 on glioblastoma cells and mice. Methods: Methyl Thiazolyl Tetrazolium (MTT) was applied for examining the viabilities of U87 and U251 cells, as well as IC50 values of temozolomide (TMZ). LncRNA DLK1-35 expressions were detected using RT-qPCR. Proliferation and apoptosis of TMZ-resistant U251 (U251 TR) cells were evaluated using colony formation and flow cytometry, respectively. Western blot was applied to analyze O6-methylguanine-DNA methyltransferase (MGMT) protein expressions. The xenograft model was used for detecting the weight and volume of tumors in mice. Results: TMZ treatment suppressed the viabilities of glioblastoma cells dose-dependently. Moreover, TMZ-resistant glioblastoma cells had higher IC50 values. lncRNA DLK1-35 was upregulated in TMZ-resistant cells while the suppression of lncRNA DLK1-35 caused low proliferation and a higher apoptosis rate. Moreover, MGMT was also inhibited by lncRNA DLK1-35 downregulation. Additionally, the weight and volume of tumors in mice were also inhibited with the knockdown of lncRNA DLK1-35. Conclusion: Knockdown of lncRNA DLK1-35 inhibited MGMT to decrease the TMZ resistance in vitro and in vivo in glioblastoma.

Rationale: Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma. Patient concerns and diagnoses: A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy. Interventions: The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane. Outcomes: After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety. Lessons: In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab.

MicroRNA-10a-5p overexpression suppresses malignancy of colon cancer by regulating human liver cancer fibroblasts

MicroRNAs (miRs) carried in exosomes serve an important role in the pre‑metastatic microenvironment and in intercellular interactions. However, the function of exosomal‑miR‑10a derived from primary colorectal cancer (CRC) cells on fibroblasts in the lung metastatic microenvironment of patients with CRC remains unclear. Reverse transcription‑quantitative PCR was performed using samples from patients with CRC, and demonstrated that the expression levels of miR‑10a were significantly lower in serum and cancer tissue samples from patients with CRC compared with in serum from healthy individuals and paired non‑cancerous tissues, respectively. In addition, the expression levels of miR‑10a were inversely associated with the invasion depth of CRC. Exosomal‑miR‑10a derived from CRC cells reduced the proliferative and migratory activities of primary normal human lung fibroblasts (NHLFs), and the expression levels of IL‑6, IL‑8 and IL‑1β in NHLFs. The present study provided insight into the phenotypic alterations of NHLFs induced by exosomal‑miR‑10a derived from CRC cells, which may aid understanding of the mechanism underlying the process of CRC lung metastasis.

MicroRNAs (miRs) have been reported to be associated with the development of numerous types of cancer. However, the function of miRs in human ovarian carcinoma chemoresistance remains largely undefined. In the present study, cell chemotherapy combined with a Cell Counting Kit-8 assay demonstrated that miR-20a performed important roles in ovarian cancer cells chemoresistance. Flow cytometry, cellular proliferation assays and Transwell assays results revealed that the proliferation and migration rates of OVCAR3/DDP cells were increased in comparison with parental cells. Western blot analysis results suggested that epithelial-mesenchymal transition (EMT) activated by miR-20a contributed to OVCAR3/DDP cell migration. The present study highlighted the importance of miR-20a in regulating the chemoresistant properties of OVCAR3 cells and promoting cisplatin-resistant cell migration by activating EMT. The results of present study may therefore provide novel insights into reversing the chemoresistance of ovarian cancer and improving its treatment.