m6A Writer METTL3-Mediated lncRNA LINC01125 Prevents the Malignancy of Papillary Thyroid Cancer.

BACKGROUND: Long non-coding RNA (lncRNA) LINC01125 is an anti-tumor factor in a variety of tumors, and regulates cancer cell function. However, its function and mechanism of N6-methyladenosine (m6A) modification in papillary thyroid cancer (PTC) tumorigenesis remain unclear. AIMS: This study aimed to reveal the function and m6A modification of LINC01125 in PTC tumorigenesis. METHODS: The LINC01125 and methyltransferase-like 3 (METTL3) levels in PTC cells and tissues was assessed by qRT-PCR. The binding relationship among LINC01125 and METTL3 was determined by MeRIP, Pearson, bioinformatics, and RNA stabilization analysis. Transwell assays were performed to confirm the changes of PTC cell migration and invasion. Cell proliferation was revealed by CCK-8 as well as colony formation assays. RESULTS: Low expression of LINC01125 and METTL3 was identified in PTC. LINC01125 was a downstream target of METTL3-mediated m6A modification and was stably upregulated via METTL3. Cell invasion, migration, viability, and colony formation levels were decreased when LINC01125 or METTL3 was upregulated. Inhibition of LINC01125 had the opposite impact, promoting cell proliferation and metastasis, and reversing METTL3 overexpression-resulted cell malignancy suppression. CONCLUSIONS: Overall, this study proved that the m6A modification of LINC01125 was mediated by METTL3 and LINC01125 inhibited cell invasion, migration and proliferation, thereby suppressing the development of PTC. This points to the LINC01125-m6A-METTL3 axis as a possible prospective target for future treatment of PTC.

Circular RNA SMARCA5 inhibits cholangiocarcinoma via microRNA-95-3p/tumor necrosis factor receptor associated factor 3 axis.

Enhancing research indicatedthat circular RNA (circRNA) acted a critical part in cholangiocarcinoma (CHOL) development. This research aims to discover the role of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) in CHOL bio-progression, which has been proved to be downregulated in CHOL tissues. In this study, quantitative reverse transcription polymerase chain reaction was used to reveal the level and linkage of circRNA SMARCA5, miRNA-95-3p and TNF receptor-associated factor 3 gene (TRAF3) in CHOL tissues and cancer cells. The target sites of circRNA SMARCA5 and miRNA-95-3p were forecast by Starbase, and Targetscan was conducted to forecast the potential linkage points of TRAF3 and miRNA-95-3p, and which is affirmed by double luciferase reporter assay. CCK-8 and flow cytometry assay was carried to indicate cell viability. And apoptosis-related protein was counted by caspase3 activity and Western blot assay. CircRNA SMARCA5 was downregulated in CHOL cell lines and cancer samples. Besides, over-expression of SMARCA5 inhibited cell growth and promoted apoptotic rate. Dual-luciferase reporter assays presented that miRNA-95-3p could link with circRNA SMARCA5. Moreover, miRNA-95-3p was discovered highly expressed in CHOL. Interference of miRNA-95-3p repressed cell proliferation and raised the apoptosis. Importantly, TRAF3 was validated to be a downstream of miRNA-95-3p. Strengthen of miRNA-95-3p reversed the inhibitory impact of circRNA SMARCA5-plasmid transfection, and the results of miRNA-95-3p inhibitor were reversed by si-TRAF3. CircRNA SMARCA5 is involved in CHOL development by interosculating miRNA-95-3p/TRAF3 axis and may become a novel approach for treating CHOL.

LncRNA LINC00969 modified by METTL3 attenuates papillary thyroid cancer progression in an m6A-dependent manner.

BACKGROUND: The long non-coding RNA (lncRNA) LINC00969 is involved in human disease progression, and n6-methyladenosine (m6A) modification of lncRNAs in cancer has been proven to be a key regulatory mechanism. However, our understanding of its effects and mechanisms of action in papillary thyroid carcinoma (PTC) remains limited. OBJECTIVES: This study aimed to elucidate the role of methyltransferase-like 3 (METTL3)-induced m6A modification of LINC00969 in PTC tumorigenesis. MATERIAL AND METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze LINC00969 and METTL3 mRNA levels in PTC. The regulation of LINC00969 by METTL3 was confirmed using cell function experiments, molecular biology assays and bioinformatics analysis. LINC00969 stabilization analysis was performed to verify the regulatory roles of METTL3 and LINC00969. RESULTS: LINC00969 expression was downregulated in PTC tissues. Increased LINC00969 expression inhibited the invasion, growth and migration of PTC cells. METTL3 downregulation in PTC mediated the m6A modification of LINC00969, increasing its stability. Furthermore, METTL3 levels were downregulated in PTC, and its silencing partially reversed the inhibitory effect of LINC00969 overexpression on PTC cell malignancy. CONCLUSIONS: LINC00969 overexpression inhibits PTC cell malignancy via METTL3-mediated m6A modification. These findings suggest that METTL3-m6A-LINC00969 is a promising therapeutic target for PTC.

Sepsis risk factors associated with HIV-1 patients undergoing surgery.

Recent developments in the treatment of HIV-1 have improved the disease prognosis from a terminal disease to a chronic disease. The number of HIV-1-infected patients who require surgery has become more common. The main threat to HIV-1-infected patients following surgery is the development of sepsis. In this study, we collected a large number of clinical recordings of HIV-1-infected patients from two hospitals in China, specializing in HIV-1 treatment in order to summarize the risk indicators of sepsis in HIV-1-infected patients. We compared the significant risk indicators between the sepsis and non-sepsis groups. Using logistic regression based on the indicators of four separate surgery-based diseases, we generally found that low CD4 and hypoalbuminemia counts prior to surgery were the significant risk factors for developing sepsis. The morbidity of sepsis in trauma patients was approximately 10 times higher than the dysfunction group, whereas the tumor and the infection groups were approximately 1.5 and 2 times higher, respectively. Based on the comparison between the sepsis and non-sepsis groups for each surgery-based disease, we found that the severity of trauma is a critical risk factor for trauma patients; therefore, limiting the size of the wound during surgery is crucial. HIV-1-infected patients often develop postoperative sepsis due to immunodeficiency and complications due to the surgery. We hope that this study can help to reduce the risk of developing sepsis due to surgery and improve the survival rate of HIV-1-infected patients.