a-nursing-intervention-combining-case-management-cbt-for

A Nursing Intervention Combining Case Management and CBT for Postoperative NSCLC Patients: Effects on Anxiety, Depression, and Quality of Life

Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. ...

Xuchang Central Hospital

N6-methyladenosine (m6A) is the most common posttranscriptional RNA modification and plays significant roles in physiological and pathological progression. Here, we probed the functions and mechanism of the m6A reader YTH domain containing 2 (YTHDC2) in Lung Adenocarcinoma (LUAD) tumorigenesis. Levels of genes and proteins of YTHDC2 and Mitochondrial ribosomal protein L7/L12 (MRPL12) were assayed by quantitative real-time polymerase chain reaction, western blotting and Immunohistochemistry (IHC) analyses. In vitro analysis was conducted using 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and transwell assays, respectively. In vivo assay was performed by using the mouse lung adenocarcinoma model. The methylated RNA immunoprecipitation (MeRIP) assay was used to detect the m6A modification profile of MRPL12 mRNA. YTHDC2 was lowly expressed in lung adenocarcinoma tissues and cells. Overexpression of YTHDC2 suppressed the proliferation, invasion and migration of lung adenocarcinoma cells, but induced cell apoptosis. As expected, forced expression of YTHDC2 hindered lung adenocarcinoma tumor growth in vivo. Mechanistically, YTHDC2 preferentially bound to m6A-modified MRPL12 mRNA and destabilized its expression. MRPL12 was highly expressed in lung adenocarcinoma tissues and cells, and MRPL12 silencing repressed the growth and mobility of lung adenocarcinoma cells. Moreover, MRPL12 upregulation attenuated the anticancer activity of YTHDC2 in lung adenocarcinoma cells. In vivo assay also showed YTHDC2 suppressed tumor growth in the lung adenocarcinoma mouse model via downregulating MRPL12. The m6A reader YTHDC2 repressed lung adenocarcinoma tumorigenesis by destabilizing MRPL12 in an m6A-dependent manner.

The m6A Reader YTHDC2 Suppresses Lung Adenocarcinoma Tumorigenesis by Destabilizing MRPL12.

Objective To investigate the regulatory effect of tumor necrosis factor-α-induced protein-8-like factor 2 (TIPE2) on the phenotype of lung cancer tumor-associated macrophages (TAM) and its influence on the stemness of lung cancer cells. Methods Mouse macrophage cell line RAW264.7 was cultured and infected with either LV-TIPE2 lentivirus or negative control LV-NC lentivirus. The TIPE2 expression in infected cells was assessed by real-time quantitative PCR (RT-qPCR) and Western blotting to verify transfection efficiency. The infected RAW264.7 cells were co-cultured with lung cancer cell line A549, and were divided into four groups: control group (RAW264.7 cells or A549 cells cultured alone), TAM group (RAW264.7 cells co-cultured with A549 cells), LV-NC group (RAW264.7 cells infected with LV-NC and co-cultured with A549 cells), LV-TIPE2 group (RAW264.7 cells infected with LV- TIPE2 and co-cultured with A549 cells). The RAW264.7 cells were collected after co-culture, and the expression of mannose receptor (CD206) protein of M2 macrophages was detected by cellular immunofluorescence staining. The proportions of M1 and M2 macrophages were detected by flow cytometry. After co-culture, A549 cells were collected, and their activity was assessed by CCK-8 assay. Self-renewal ability was evaluated using tumor cell pelleting experiment. The expression of stemness marker proteins-including cluster of differentiation 133 (CD133), transmembrane adhesion molecule (CD44), sex-determining region Y-box protein 2 (SOX2) and octamer-binding transcription factor 4 (OCT4)-was detected by Western blot. Results Compared with the control group or LV-NC group, the relative mRNA and protein expression levels of TIPE2 in RAW264.7 cells from the LV-TIPE2 group were significantly upregulated. Compared with the control group, the fluorescence intensity of M2-type macrophage marker CD206 protein in RAW264.7 cells from the TAM group was significantly increased, the proportion of M1-type macrophages was significantly decreased, and the proportion of M2-type macrophages was significantly increased. In contrast, compared with the TAM group, the fluorescence intensity of CD206 protein in RAW264.7 cells from the LV-TIPE2 group was significantly decreased, the proportion of M1-type macrophages was significantly increased, and the proportion of M2-type macrophages was significantly decreased. Compared with the control group, the proliferation activity of A549 cells in TAM group was significantly increased, the number of tumor pellet formation was significantly increased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly up-regulated. However, compared with the TAM group, the proliferation activity of A549 cells from the LV-TIPE2 group was significantly decreased, the number of tumor pellet formation was significantly decreased, and the relative expression levels of CD133, CD44, SOX2 and OCT4 were significantly decreased. Conclusion TIPE2 can suppress the stemness of lung cancer cells by inhibiting the polarization of macrophages to M2-type, thereby exerting an anticancer effect.

Article	Year
The m6A Reader YTHDC2 Suppresses Lung Adenocarcinoma Tumorigenesis by Destabilizing MRPL12. Molecular biotechnology\| PubMed ID: 38129673	2024
[TIPE2 inhibits the stemness of lung cancer cells by regulating the phenotypic polarization of tumor-associated macrophages]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology\| PubMed ID: 40670131	2025

Yingchuan Sun

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