HNRNPU-AS1 Regulates Cell Proliferation and Apoptosis via the MicroRNA 205-5p/AXIN2 Axis and Wnt/ß-Catenin Signaling Pathway in Cervical Cancer.

Long noncoding RNAs (lncRNAs) have key functions in modulating cervical cancer (CC) genesis and progression. This work focused on exploring lncRNA HNRNPU-AS1's function in CC and the underlying mechanism. HNRNPU-AS1, AXIN2, and microRNA 205-5p (miR-205-5p) levels in CC cases were measured through reverse transcription-quantitative PCR. The relationship between miR-205-5p and AXIN2 or HNRNPU-AS1 was validated through a dual-luciferase assay. Cell proliferation was examined by CCK-8 and cell apoptosis by colony formation and flow cytometry analysis. HNRNPU-AS1 expression loss could be observed in CC patients and cell lines, which predicted the dismal prognosis of CC cases. Moreover, it was identified that the miR-205-5p level was upregulated, which acted as an inhibitory target of HNRNPU-AS1 and AXIN2. HNRNPU-AS1 inhibited cell proliferation and promoted apoptosis. As revealed by Kaplan-Meier curve, CC cases showing low HNRNPU-AS1, high miR-205-5p, and low AXIN2 levels had the poorest prognosis. AXIN2 reversed the CC cell proliferation-promoting, apoptosis-inhibiting, and Wnt/ß-catenin signaling-activating behavior mediated by miR-205-5p or HNRNPU-AS1 knockout. In conclusion, the overexpression of lncRNA HNRNPU-AS1 suppressed CC progression by inhibiting the Wnt/ß-catenin pathway through the miR-205-5p/AXIN2 axis.

The disease stage-associated imbalance of Th1/Th2 and Th17/Treg in uterine cervical cancer patients and their recovery with the reduction of tumor burden.

BACKGROUND: Nearly all uterine cervical cancer (UCC) cases result from human papillomavirus (HPV) infection. After high-risk HPV infection, most HPV infections are naturally cleared by humoral and cell-mediated immune responses. Thus, cervical lesions of only few patients progress into cervical cancer via cervical intraepithelial neoplasia (CIN) and lead to persistent oncogenic HPV infection. This suggests that immunoregulation plays an instrumental role in the carcinogenesis. However, there was a few studies on the relation between the immunologic dissonance and clinical characteristics of UCC patients. METHOD: We examined the related immune cells (Th1, Th2, Th17, and Treg cells) by flow cytometric analysis and analyzed their relations with UCC stages, tumor size, differentiation, histology type, lymph node metastases, and vasoinvasion. Next, we quantified the Th1, Th2, Th17, and Treg cells before and after the operation both in UCC and CIN patients. RESULTS: When compared with stage I patients, decreased levels of circulating Th1 cells and elevated levels of Th2, Th17, and Treg cells were detected in stage II patients. In addition, the imbalance of Th1/Th2 and Th17/Treg cells was related to the tumor size, lymph node metastases, and vasoinvasion. We found that immunological cell levels normalized after the operations. In general, immunological cell levels in CIN patients normalized sooner than in UCC patients. CONCLUSIONS: Our findings suggested that peripheral immunological cell levels reflect the patient's condition.

Smad4 induces cell death in HO-8910 and SKOV3 ovarian carcinoma cell lines via PI3K-mTOR involvement.

IMPACT STATEMENT: This study investigated the effect and mechanism of Smad4 in ovarian carcinoma (OC) cell viability and demonstrated that Smad4 acted as a tumor suppressor in OC, which may contribute to the understanding of molecular mechanisms underlying OC occurrence and progression. Smad4 expression was decreased in the OC specimens, but Smad4 recovery in the OC cell lines impaired the survival and viability of OC cells by increasing autophagy and apoptosis. Further investigation showed that Smad4 interacted with the P85 subunit of PI3K and caused deactivation of the PI3K/mTOR pathway. Therefore, Smad4 could be considered as a target in cancer therapy due to its regulatory effect in OC carcinogenesis.

Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer.

Uterine cervical cancer (UCC) causes more than one quarter of a million deaths per year in many developing countries. Nearly all cases of cervical cancer result from infection with the human papillomavirus. After high-risk HPV infection, most HPV infections are cleared naturally as a result of humoral and cell-mediated immune responses. Only a limited number of patients' cervical lesions progress through CIN to cervical cancer, from persistent oncogenic human papillomavirus (HPV) infection. This indicated that immunoregulation may play a central role in the HPV-induced carcinogenesis. However, the natural history of clearance of a cervical HPV infection or its progression to a UCC needs clarification. We examined the related immune cells (Th1, Th2, Th17 and Treg cells) and related immune factors (INF-γ, IL-4, IL-10, IL-17, IL-23, TGF-ßI) of UCC patients, CIN patients, HPV infected patients, and healthy controls. Compared with healthy controls, patients with UCC or CIN had a lower proportion of Th1 cells, and a higher proportion of Th2, Th17, and Treg cells. IL-4, IL-10, IL-17, IL-23 and TGF-ßI concentrations in serum were found to be increased from patients with UCC or CIN, while INF-γ concentration in serum with UCC or CIN decreased. Our findings suggested that there were attractive imbalances of Th1/Th2 and Th17/Treg cells in UCC and CIN patients. HPV persistent infection induced an immunologic dissonance, and the degree of imbalance is aggravated with the progression of the disease.

Impact of IL-22 and IL-22 receptor alpha 1 polymorphisms on preeclampsia risk in Chinese Han women.

Previous studies have indicated that an increased inflammatory response plays an important role in preeclampsia (PE), and rising levels of interleukin (IL)-22 can trigger inflammation and hyperproliferation, leading to increased production of several pro-inflammatory cytokines such as IL-1, IL-6, and IL-8. We aimed to investigate the association between polymorphisms of IL-22 and IL-22 receptor alpha 1 gene (IL-22RA1) and PE in Chinese Han population. Single nucleotide polymorphisms (SNPs) rs2227485 in IL-22 and rs3795299 in IL-22RA were genotyped by Taqman real-time PCR in 1071 PE patients and 1263 control subjects. Differences in genetic distribution were compared between two groups using the chi-square test. Significant differences were observed in genotypic and allelic frequencies of IL-22RA1 rs3795299 between healthy controls and PE patients (P < 0.001 by genotype; P = 0.001, odds ratio = 1.253, 95% confidence interval 1.103-1.424 by allele). There were also significant differences in genotypic and allelic frequencies of rs3795299 between late-onset/mild PE and control groups. In addition, we found obvious statistic difference for the allele of early-onset PE/the genotype of late-onset PE and control subgroups for IL-22 rs2227485. IL-22 rs2227485 and IL-22RA1 rs3795299 may be associated with the development of PE in Chinese Han population. However, further validation is required in other populations, as well as an evaluation of the association of other SNPs in IL-22 and IL-22RA1 with PE.

The Association of CARD8 rs2043211 Polymorphism with Preeclampsia in the Chinese Han Population.

OBJECTIVE: The purpose of our study was to investigate the association between polymorphism of rs2043211 in CARD8 and susceptibility to preeclampsia (PE) in the Chinese Han population. METHODS: 261 PE patients and 451 controls were genotyped for rs2043211 with the method of TaqMan allele discrimination assays. Clinical data were collected to perform genotype-phenotype analysis. RESULTS: Our study suggested that the rs2043211 variant was associated with the development of PE in the Chinese Han population. The genotypic and allelic frequencies differed significantly between the two groups (x03C7;2 = 8.198, p = 0.017 by genotype; x03C7;2 = 6.741, p = 0.009 by allele). The T allele was the risk allele for predisposition to PE (OR = 1.331, 95% CI 1.072-1.652). CONCLUSION: The polymorphism of rs2043211 in CARD8 may be a relevant host susceptibility factor for the development of PE in the Chinese Han population.

Do obsessive-compulsive disorder and Tourette syndrome share a common susceptibility gene? An association study of the BDNF Val66Met polymorphism in the Chinese Han population.

OBJECTIVES: We explored the association between the BDNF Val66Met polymorphism and susceptibility to both obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) in the Chinese Han population. METHODS: Genotyping for the BDNF Val66Met polymorphism was performed in 321 OCD patients and 426 healthy control subjects and case-control association study data were analysed. Additionally, we evaluated the genetic contribution of this variant in 331 TS patients (including 267 TS trios) and 519 controls using the transmission disequilibrium test (TDT) and case-control study. RESULTS: A statistically significant difference was found in the genetic contribution of the BDNF Val66Met polymorphism between both the OCD (χ(2) = 7.50, P = 0.023 by genotype; χ(2) = 6.67, P = 0.01 by allele) and TS (χ(2) = 6.76, P = 0.03 by genotype; χ(2) = 4.27, P = 0.04 by allele), and control groups. TDT and GHRR analysis for TS trios also showed a significant transform disequilibrium of this polymorphism (TDT: χ(2) = 3.96, P = 0.05; HHRR: χ(2) = 4.33 P = 0.04; GHRR: χ(2) = 5.74, P = 0.02; χ(2) = 0.98, P = 0.37). There was also a significant gender trend between patients and controls in female cases for OCD and in male cases for TS. CONCLUSIONS: Our study supports the involvement of the BDNF Val66Met polymorphism as a common genetic susceptibility for OCD and TS in the Chinese Han population, showing specific gender trends.