SOX2-associated signaling pathways regulate biological phenotypes of cancers.

SOX2 is a transcription factor involved in multiple stages of embryonic development. In related reports, SOX2 was found to be abnormally expressed in tumor tissues and correlated with clinical features such as TNM staging, tumor grade, and prognosis in patients with various cancer types. In most cancer types, SOX2 is a tumor-promoting factor that regulates tumor progression and metastasis primarily by maintaining the stemness of cancer cells. In addition, SOX2 also regulates the proliferation, apoptosis, invasion, migration, ferroptosis and drug resistance of cancer cells. However, SOX2 acts as a tumor suppressor in some cases in certain cancer types, such as gastric and lung cancer. These key regulatory functions of SOX2 involve complex regulatory networks, including protein-protein and protein-nucleic acid interactions through signaling pathways and noncoding RNA interactions, modulating SOX2 expression may be a potential therapeutic strategy for clinical cancer patients. Therefore, we sorted out the phenotypes related to SOX2 in cancer, hoping to provide a basis for further clinical translation.

Zinc oxide nanoparticles promotes liver cancer cell apoptosis through inducing autophagy and promoting p53.

OBJECTIVE: Emerging evidence has highlighted the promising potential of the application of Zinc Oxide nanoparticles (nano-ZnO) but the mechanism by how it functions in liver cancer remains elusive. We aimed to explore the effect of nano-ZnO on liver cancer cells. MATERIALS AND METHODS: Liver cancer cells Huh7 cells were transfected with GFP-LC3, and then, treated with DMSO, Sorafenib, and nano-ZnO respectively to set blank group, Sorafenib control group, and nano-ZnO group followed by the analysis of the expression of GFP-LC3, p53, and Caspase by Western blot and RT-qPCR, cell apoptosis and viability by flow cytometry and CCK-8 assay. RESULTS: With a diameter of nano-ZnO 14.13±0.92 nm, the amount of GFP-LC3 protein was increased after treatment of nano-ZnO. Besides, the expressions of GFP-LC3, p53, and Caspase in Sorafenib group and nano-ZnO group were significantly higher than that of control group, while their levels were highest in nano-ZnO group (p<0.05). In nano-ZnO group, the values of D450nm at 24 h, 48h, and 72 h were 0.56±0.06, 0.39±0.05, and 0.22±0.04, respectively, and the apoptotic rate (83.11±2.79%) was significantly lower than that of blank group and control group. CONCLUSIONS: Nano-ZnO induced autophagy, upregulated the p53 gene, and facilitated the apoptosis of liver cancer cells, indicating that nano-ZnO might be a therapeutic approach for the treatment of liver cancer patients.

Analysis of NudCD1 and NF-κΒ in the early detection and course evaluation of renal cancer.

OBJECTIVE: Early detection and effective evaluation are helpful for renal cancer diagnosis and treatment. NudCD1 and NF-κΒ are abnormally expressed in tumors and inflammations. However, their role in early detection and course evaluation of renal cancer has not been reported. PATIENTS AND METHODS: The serum of clinically diagnosed renal cancer patients and healthy volunteers (control group) were collected to measure the expressions of NudCD1 and NF-κΒ mRNA by Real time PCR. RESULTS: NudCD1 and NF-κΒ mRNA in renal cancer patients were significantly upregulated compared to controls (p<0.05). NudCD1 was positively correlated with tumor diameter, TNM stage, lymph node metastasis, degree of differentiation, and distant metastasis (p<0.05); whereas, NF-κΒ was positively related to TNM stage, lymph node metastasis, and distant metastasis (p<0.05) but not to tumor diameter and differentiation degree. NudCD1 and NF-κΒ were positively correlated. The combined detection improved the diagnostic specificity and sensitivity of renal cancer. CONCLUSIONS: The expression of NudCD1 and NF-κΒ is increased in renal cancer and is correlated with renal cancer clinicopathological characteristics. The combined detection of NudCD1 and NF-κΒ can improve the early diagnosis of kidney cancer.

MiR-24 inhibits oligodendrocyte precursor cell differentiation after spinal injury by targeting adrenal medulla.

OBJECTIVE: Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) that provide nutrients to neurons. Adrenal medulla is (ADM) involved in nerve damage. MiR-24 participates in various diseases. However, the regulation and mechanism of miR-24 in oligodendrocyte precursor cell differentiation after spinal injury is unclear. MATERIALS  AND METHODS: Wistar rats were divided into sham operation group and model group. Real Time-PCR detects miR-24, PDGFRa and NG2 and MBP expression. OPC cells were cultured and divided into control group, miR-24 group, and si-miR-24 group followed by analysis of miR-24 expression by Real Time-PCR, expression of PDGFRa, NG2 and MBP by Western blot, as well as ADM content and secretion of IL-6 and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of miR-24, PDGFRa, and NG2 was increased in the model group and MBP and ADM expression was decreased with increased secretion of IL-6 and TNF-α. Compared with control group, the difference was statistically significant (p<0.05). Upregulation of miR-24 promoted the expression of PDGFRa and NG2, decreased MBP and ADM level, and increased IL-6 and TNF-α secretion. Compared with control group, the difference was statistically significant (p<0.05). Downregulation of miR-24 reversed the above changes, and the difference was statistically significant (p<0.05). CONCLUSIONS: MiR-24 expression is increased in spinal injury. Upregulation of miR-24 expression reduces adrenal medulla expression and inhibits oligodendrocyte precursor cell differentiation.

Down-regulation of miR-29a facilitates apoptosis of colorectal carcinoma cell SW480 and suppresses its Paclitaxel resistance.

OBJECTIVE: PTEN can suppress PI3K/AKT activity, and regulate cell proliferation, apoptosis, and drug resistance. The previous study showed that up-regulation of miR-29a played an essential role in the occurrence of colorectal carcinoma. This study aimed to investigate the role and related mechanism of miR-29a in mediating Paclitaxel sensitivity of colorectal carcinoma cells. MATERIALS AND METHODS: Bioinformatics analysis was performed to study the existence of binding sites between miR-29a and targeting gene mRNA. Dual luciferase reporter assay was conducted to validate the targeted regulation. The expressions were compared between CCD841 CoN cells, colorectal carcinoma cell line SW480, and drug-resistant cell line SW480/Paclitaxel. Cell apoptosis and proliferation were measured by flow cytometry. In vitro cultured SW480/Paclitaxel cells were transfected with miR-29a or pcDNA3.1-PTEN. MiR-29a and PTEN expressions were measured by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blot, followed by flow cytometry on the detection of cell apoptosis as well as proliferation assay. RESULTS: A targeted regulatory relationship existed between miR-29a and PTEN. Comparing to CCD841 CoN cells, high level of miR-29a and decreasing expression of PTEN were found in SW480 cells. Moreover, further higher miR-29a and lower PTEN expressions were observed in SW480/Paclitaxel cells. Paclitaxel remarkably inhibited proliferation and facilitated apoptosis of SW480 cells but not SW480/Paclitaxel cells. Transfection of miR-29a inhibitor or pcDNA3.1-PTEN remarkably elevated PTEN expression, suppressed p-AKT expression, weakened proliferation, and enhanced apoptosis of SW480/Paclitaxel cells. CONCLUSIONS: Our data demonstrated that suppression of miR-29a enhanced PTEN expression, inhibited cancer cell proliferation, facilitated apoptosis, and weakened drug resistance, which provides academic basis for the treatment of colorectal cancer.

Investigation of PD-1H in DEN-induced mouse liver cancer model.

OBJECTIVE: Immune therapy has recently become a novel strategy for treating liver cancer, making it of critical importance to identify novel targets for treatment. Programmed death-1 homology (PD-1H) is one newly discovered negative co-stimulating molecule, and plays important regulatory roles in suppressing T cell activation. However, the expression or function of PD-1H in liver tumors has not been reported. MATERIALS AND METHODS: Liver cancer tissues were collected from The Cancer Genome Atlas (TCGA) (http://tcga-data.nci-nih.gov). This study then utilized diethylnitrosamine (DEN) induced liver cancer mice, on which PD-1H monoclonal antibody and PD-1H extra-cellular Fc domain fusion protein were injected intraperitoneal. General status, gross morphology of liver tissues was examined, followed by hematoxylin-eosin (HE) staining and plotting survival curve. RESULTS: Among TCGA samples, PD-1H expression was significantly elevated. Induced liver cancer mice showed depressed mental status, early onset of hepatitis and liver cirrhosis. Five mice dead in model group (mortality=33.33%). No natural death occurred in control group. Injection of PD-1H-Fc-Ig fusion and PD-1H monoclonal antibody improved the condition to certain extents, with morality at about 20%. Comparing to DEN group, combined treatment group showed significantly fewer tumor lesion on liver surface, with increased body weight and lower liver-body weight ratio. HE staining showed significantly elevated ratio of normal cells in combined treatment group, although large amounts of cancer cells still existed. CONCLUSIONS: Blocking of PD-1H signal pathway could suppress liver cancer cell growth, decrease mouse mortality, indicating promising application of PD-1H in tumor immune therapy.