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Abstract Background Nasopharyngeal carcinoma (NPC) is characterized by pronounced metastatic and invasive properties. Emerging research has elucidated that circular RNAs (circRNAs) are intricately associated with the pathogenesis of NPC, potentially serving as critical mechanisms in tumorigenesis and as promising therapeutic targets for NPC. Methods The expression levels of circRNAs were analyzed in NPC using reverse transcription quantitative PCR (RT-qPCR). Wound healing, transwell, and clone formation assays were conducted to examine the metastatic potential of NPC. Cell proliferation and apoptosis assays were performed to evaluate cell proliferation and survival. 3D spheroid cultures, RNA pull-down, LC-MS, RNA-sequencing, and luciferase reporter assays were carried out to examine the mechanisms of circPPP1CB in NPC progression. NPC xenograft tumor models were estimated to verify the mechanisms of circPPP1CB in tumor growth and metastasis of NPC in vivo. Results CircPPP1CB subtype, hsa_(c)irc₀007439, that was more highly expressed in NPC patients with distant metastasis than in those without distant metastasis. Hsa_(c)irc₀007439 overexpression specifically promotes proliferation and inhibits the apoptosis of NPC cells. Further experiments indicated that hsa_(c)irc₀007439 overexpression was correlated with increased tumor growth and distant metastasis of NPC cells. Mechanistically, hsa_(c)irc₀007439 upregulated KRT1 expression by acting as a sponge for miR-1275 and miR-1293. This led to increased proliferation and metastatic progression in NPC by activating the JAK/STATs signaling pathway. Conclusions This study is the first to demonstrate that hsa_(c)irc₀007439 functions as a competitive endogenous RNA to upregulate KRT1 expression, thereby promoting the metastasis of NPC, suggesting that hsa_(c)irc₀007439 serve as a potential diagnostic biomarker and therapeutic target for NPC.

Background/Aims: Drug resistance remains a main obstacle to the treatment of non- small cell lung cancer (NSCLC). The aim of this study was to identify the expression profiles of microRNAs (miRNAs) in drug-resistant NSCLC cell lines. Methods: The expression profiles of miRNAs in drug-resistant NSCLC cell lines were examined using miRNA sequencing, and the common dysregulated miRNAs in these cell lines were identified and analyzed by bioinformatics methods. Results: A total of 29 upregulated miRNAs and 36 downregulated miRNAs were found in the drug-resistant NSCLC cell lines, of which 26 upregulated and 36 downregulated miRNAs were found to be involved in the Ras signaling pathway. The expression levels, survival analysis, and receiver operating characteristic curve of the dysregulated miRNAs based on The Cancer Genome Atlas database for lung adenocarcinoma showed that hsa-mir-192, hsa-mir-1293, hsa-mir-194, hsa-mir-561, hsa-mir-205, hsa-mir-30a, and hsa-mir-30c were related to lung cancer, whereas only hsa-mir-1293 and hsa-mir-561 were not involved in drug resistance. Conclusion: The results of this study may provide novel biomarkers for drug resistance in NSCLC and potential therapies for overcoming drug resistance, and may also reveal the potential mechanisms underlying drug resistance in this disease.

Background Nasopharyngeal carcinoma (NPC) is characterized by pronounced metastatic and invasive properties. Emerging research has elucidated that circular RNAs (circRNAs) are intricately associated with the pathogenesis of NPC, potentially serving as critical mechanisms in tumorigenesis and as promising therapeutic targets for NPC. Methods The expression levels of circRNAs were analyzed in NPC using reverse transcription quantitative PCR (RT-qPCR). Wound healing, transwell, and clone formation assays were conducted to examine the metastatic potential of NPC. Cell proliferation and apoptosis assays were performed to evaluate cell proliferation and survival. 3D spheroid cultures, RNA pull-down, LC-MS, RNA-sequencing, and luciferase reporter assays were carried out to examine the mechanisms of circPPP1CB in NPC progression. NPC xenograft tumor models were estimated to verify the mechanisms of circPPP1CB in tumor growth and metastasis of NPC in vivo. Results CircPPP1CB subtype, hsa_circ_0007439, that was more highly expressed in NPC patients with distant metastasis than in those without distant metastasis. Hsa_circ_0007439 overexpression specifically promotes proliferation and inhibits the apoptosis of NPC cells. Further experiments indicated that hsa_circ_0007439 overexpression was correlated with increased tumor growth and distant metastasis of NPC cells. Mechanistically, hsa_circ_0007439 upregulated KRT1 expression by acting as a sponge for miR-1275 and miR-1293. This led to increased proliferation and metastatic progression in NPC by activating the JAK/STATs signaling pathway. Conclusions This study is the first to demonstrate that hsa_circ_0007439 functions as a competitive endogenous RNA to upregulate KRT1 expression, thereby promoting the metastasis of NPC, suggesting that hsa_circ_0007439 serve as a potential diagnostic biomarker and therapeutic target for NPC.

Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified. miR-1293 expression and its association with LUAD patients' clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model. We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients' pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression . miR-1293 promoted the proliferation, migration and invasion of LUAD cells targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.

Tissue inhibitor of metalloproteinases 1 (TIMP-1) is a glycosylated protein with multiple activities in the regulation of biological processes, such as cell growth and apoptosis as well as tumor invasion and metastasis. Bioinformatics analysis using TargetScan and miRanda suggested tissue inhibitors of TIMP-1 are among the targets of miR-1293. To confirm this, we cloned both wild-type and mutant TIMP-1 3′UTR fragments by overlap extension PCR, constructed the recombinant plasmids pGL3-TIMP-1-wt, -mut, and pcDNA 3.1(+)/TIMP-1-CDS and, respectively, co-transfected them into 293T cells with the miR-1293 inhibitor, mimics or the miR inhibitor-NC using a BTX ECM 2001 square-wave electroporator. We used a luciferase assay to investigate binding of miR-1293 to the 3′UTR of TIMP-1. Effects on the levels of the TIMP-1 protein were analyzed by Western blot experiments. The luciferase reporter assay showed a statistically significant ( P  < 0.05) upregulation of activity. Western blot analysis showed a significant increase of expression of the TIMP-1 gene co-transfected with the miR-1293 inhibitor, and demonstrated direct binding of miR-1293 to the 3′UTR of TIMP-1. In this study, we identified TIMP-1 as a novel direct target for miR-1293, which provides the basis for further study of the multifunctional mechanisms of miR-1293 and TIMP-1 in the regulation of a variety of diseases.