To investigate the prognostic value of N6-methyladenosine (m6A)-, 5-methylcytosine (m5C)-, and N1-methyladenosine (m1A)-related genes in cervical cancer (CESC) and predicting immunotherapy response...

Background/aims: Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC. Methods: In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs–microRNAs (miRNAs)–messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network. Results: Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P<0.05). The upregulated hsa_circ_0039569 and hsa_circ_0001610 and downregulated hsa_circ_0000437, hsa_circ_0001776, and hsa_circ_0009043 were validated by qRT-PCR analysis. Using bioinformatical methods, we found that hsa_circ_0039569 has the MRE of hsa-miR-542-3p and hsa-let-7c-5p. Hsa-miR-542-3p and hsa-let-7c-5p were downregulated in the grade 3 EC validated by qRT-PCR analysis. In the clinicopathological parameters, the expression level of hsa_circ_0039569 was significantly correlated with tumor differentiation (P=0.001). Conclusion: This is the first study demonstrated that there were a lot of differences between the tissue of the grade 3 EC and adjacent non-cancerous endometrial in circRNA expression and may offer novel molecular candidates for diagnosis and clinical treatment of the grade 3 EC.

Osteosarcoma (OS) is a type of primary malignant bone tumor with a high propensity for local recurrence and distant metastasis. A previous study showed Snail‑1 is highly expressed in OS cells. The present study aimed to investigate the association between the transcription factor Snai1 and E‑cadherin in OS. SaOS2 OS cells were transfected either with a plasmid expressing short hairpin RNA (shRNA) specific for the Snai1‑1 gene (SaOS2‑shRNA) or a negative control plasmid (SaOS2‑Mock). The expression levels of E‑cadherin and Snai1‑1 in the transfected and control cells were determined by quantitative polymerase chain reaction and western blot analysis. In addition, the study was extended to evaluate the migratory and invasive properties of the cells through a Transwell experiment. The results show that E‑cadherin was expressed at a high level in the SaOS2‑shRNA cells, which were much less migratory and invasive than the control cells. Overexpression of Snai1‑1 in OS is associated with tumor progression, possibly through the suppression of E‑cadherin expression and induction of the process of epithelial‑mesenchymal transition, which contributes to the proceeding invasion and metastasis of OS cells.

Background/Aims: The present study aimed to analyze the mechanisms by which periodic mechanical stress is translated into biochemical signals, and to verify the important role of signaling molecules including phosphatidylinositol-3-kinase (PI3K)-Akt, protein kinase C (PKC), and epidermal growth factor receptor (EGFR) in chondrocyte proliferation. The effects of periodic mechanical stress on the mitogenesis of chondrocytes have been studied extensively in recent years. However, the mechanisms underlying the ability of chondrocytes to sense and respond to periodic mechanical stress need further investigation. Methods: Two steps were undertaken in the experiment. In the first step, the cells were pretreated with shRNA targeted to Akt or EGFR or PKCδ or control scrambled shRNA. Moreover, they were pretreated with LY294002, GF109203X, Gö6976, rottlerin, and AG1478. They were maintained under static conditions or periodic mechanical stress for 3 days, 8 h per day, prior to direct cell counting and CCK-8 assay, respectively. In the second step, the cells were pretreated with shRNA targeted to Akt or EGFR or PKCδ or control scrambled shRNA. Moreover, they were pretreated with LY294002, AG1478, and rottlerin. They were maintained under static conditions or periodic mechanical stress for 1 h prior to Western blot analysis. Results: Proliferation was inhibited by pretreatment with PKC or PKCδ inhibitor GF109203X or rottlerin and by short hairpin RNA (shRNA) targeted to PKCδ, but not by PKCα inhibitor Gö6976 in chondrocytes in response to periodic mechanical stress. Meantime, rottlerin and shRNA targeted to PKCδ also attenuated EGFR, Akt, and ERK1/2 activation. Furthermore, inhibiting EGFR activity by AG1478 and shRNA targeted to EGFR abrogated chondrocyte proliferation and phosphorylation levels of Akt and extracellular signal-regulated kinase (ERK)1/2 subjected to periodic mechanical stress, while the phosphorylation site of PKCδ was not affected. In addition, pretreatment with the PI3K-Akt-selective inhibitor LY294002 and shRNA targeted to Akt reduced periodic mechanical stress-induced chondrocyte proliferation and phosphorylation of ERK1/2, while the phosphorylation levels of EGFR and PKCδ were not inhibited. Conclusion: These findings suggested that periodic mechanical stress promoted chondrocyte proliferation through PKCδ-EGFR-PI3K-Akt-ERK1/2. They provide a stronger viewpoint for further investigations into chondrocyte mechanobiology under periodic mechanical stress and the ways to improve the quality of tissue-engineered cartilage.

Connections between chronic inflammation and tumor development and progression are now generally accepted. Recent evidence indicates that hepatitis B is associated with several types of cancer, but whether endometrial carcinoma (EC) is included has not been reported. We analyzed HBV serum marker status in 398 patients with endometrial cancer, comparing them to 788 control women undergoing health examination. The total prevalence of HBsAg tested positive in cancer group was significantly higher than the control group (12.8% vs 6.0%, P=0.001), while positive HBsAb was significantly lower (41.2% vs 68.5%, P=0.001). Hepatitis B carriers in endometrial cancer group were also more frequent than in the control group (9.3% vs 5.5%, P=0.013). Interestingly, in the endometrial cancer group, 147 cases were HBV serum marker negative, which was also higher than in the control group (36.9% vs 15.6%, P=0.001). There may be a correlation between HBV infection and endometrial carcinoma.

Gestational choriocarcinoma ended with a successful parturition is extremely rare, especially in cases where multiple metastases occurred.A 29-year-old Chinese primigravida was admitted with vaginal bleeding at 32 gestational week, and diagnosed with gestational choriocarcinoma with vaginal, pulmonary, and cerebral metastasis after pathological, and imaging examination. At 33 gestational week, a healthy infant was delivered by cesarean section. Although no evidence of choriocarcinoma or any other forms of gestational trophoblastic diseases was found in the placenta and uterine curettages, the patient was given 7 cycles of postpartum chemotherapy. Her serum beta-human chorionic gonadotropin level fell to the normal range, and the metastatic lesions reduced. The baby is still free from diseases, and the patient reports no clinical manifestation 4 years after the hospital discharge.Despite its rapid metastases and complications, gestational choriocarcinoma still can be successfully treated by postpartum chemotherapy with the least delay.