Circ_0031242 regulates the functional properties of hepatocellular carcinoma cells through the miR-944/MAD2L1 axis.

BACKGROUND: Circular RNAs (circRNAs) possess key functions in the pathogenesis of hepatocellular carcinoma (HCC). Nonetheless, the actions of individual circRNAs in HCC remain undefined. METHODS: circ_0031242, miR-944, and MAD2L1 expression were quantified by qRT-PCR. Transwell assay was utilized to examine cell invasion and migration. Glucose consumption and lactate production were measured to assess the impact on glycolysis. The relationships among circ_0031242, MAD2L1, and miR-944 were examined via luciferase reporter assay. RESULTS: circ_0031242 was notably augmented in HCC. Loss of function of circ_0031242 hindered cell proliferation, invasion, migration, glycolysis, and promoted apoptosis, as well as impeding HCC tumor growth. circ_0031242 directly targeted miR-944. Inhibition of miR-944 counteracted the effects of si-circ_0031242 on HCC cells. Additionally, miR-944 was proved to directly target MAD2L1 in HCC cells. Moreover, the promotion of MAD2L1 was able to rescue the inhibition of high miR-944 expression on HCC cell progression. Meanwhile, circ_0031242 involved the post-transcriptional modulation of MAD2L1 through miR-944. CONCLUSION: This study suggested that circ_0031242 regulated tumor cell progression and tumor growth through the miR-944/MAD2L1 axis in HCC.

Genomic characterization of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population.

BACKGROUND: The objective of this study was to investigate genetic variations and the relationships between these genetic variations and clinicopathological features of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population. METHODS: One hundred sixty-eight patients of high-recurrence risk papillary thyroid carcinoma were recruited for this study from 2017 to 2018. Formalin-fixed paraffin-embedded tissue and the data of clinicopathological characteristics were all collected and analyzed from these patients. We used next-generation sequencing technology to investigate the targeted gene mutations and gene fusions of the pathology specimens. RESULTS: The frequency of candidate tumor driver gene mutation was 85.1% in 143 patients, including BRAF V600E mutation in 119 patients(70.8%), RET fusion in 13 patients(7.7%), TERT promoter mutations in 11 patients(6.5%), RAS (HRAS, NRAS, KRAS) gene mutations in 10 patients(6.0%), and other mutations involving TP53, PIK3CA, AKT1, PTEN and NTRK1. Concomitant presence of more than two genetic aberrations was seen in 27 patients (16.1%). Our study showed that BRAF V600E mutation is highly correlated with conventional PTC (p < 0.001), BRAF V600E and TERT promoter mutation duet was associated with older patient age (> 45, p = 0.003) and higher disease stage of III or IV (p = 0.002). RAS gene and BRAF V600E co-mutations were only seen in multifocal PTC (p = 0.015). CONCLUSION: In our high-recurrence risk PTC cohort, most patients had more than one driver gene aberration. Coexistence of BRAF V600E with TERT promoter mutations or with RAS mutations were significantly correlated with worse clinicopathological characteristics.

Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.

Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817-1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635-0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647-0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748-0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763-0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

The complete mitochondrial genome of Anopheles minimus (Diptera: Culicidae) and the phylogenetics of known Anopheles mitogenomes.

Anopheles minimus is an important vector of human malaria in southern China and Southeast Asia. The phylogenetics of mosquitoes has not been well resolved, and the mitochondrial genome (mtgenome) has proven to be an important marker in the study of evolutionary biology. In this study, the complete mtgenome of An. minimus was sequenced for the first time. It is 15 395 bp long and encodes 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and a non-coding region. The gene organization is consistent with those of known Anopheles mtgenomes. The mtgenome performs a clear bias in nucleotide composition with a positive AT-skew and a negative GC-skew. All 13 PCGs prefer to use the codon UUA (Leu), ATN as initiation codon but cytochrome-oxidase subunit 1 (COI) and ND5, with TCG and GTG, and TAA as termination codon, but COI, COII, COIII and ND4, all with the incomplete T. tRNAs have the typical clover-leaf structure, but tRNA(Ser(AGN)) is consistent with known Anopheles mtgenomes. The control region includes a conserved T-stretch and a (TA)n stretch, and has the highest A+T content at 93.1%. The phylogenetics of An. minimus with 18 other Anopheles species was constructed by maximum likelihood and Bayesian inference, based on concatenated PCG sequences. The subgenera, Cellia and Anopheles, and Nyssorhynchus and Kerteszia have mutually close relationships, respectively. The Punctulatus group and Leucosphyrus group of Neomyzomyia Series, and the Albitarsis group of Albitarsis Series were suggested to be monophyletic. The monophyletic status of the subgenera, Cellia, Anopheles, Nyssorhynchus and Kerteszia need to be further elucidated.

Sequencing and analysis of the complete mitochondrial genome in Anopheles culicifacies species B (Diptera: Culicidae).

The complete mitochondrial genome sequence of Anopheles culicifacial species B was sequenced in this study. The length of the mitochondrial genome is 15 330 bp, which contains 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a non-coding control region. The gene order and the gene composition are consistent with those previously reported for other mosquito species. The initiation codon of the PCGs complies with the ATN rule except for COI using TCG and ND5 using GTG as a start codon, and the termination codon is TAA or imcomplete, an only T. The total base composition is 40.4% A, 38.1% T, 12.4% C, and 9.1% G. The phylogenetic tree based on the sequences of 13 protein-coding genes showed that these species were classified into two clades, corresponding to the subgenus Cellia and subgenus Nyssorhynchus. An. culicifacies species B of Myzomyia Series was clustered with An. gambiae of Pyretophorus Series with a high bootstrap value of 100%. The complete mitogenome data can provide a basis for molecular identification and phylogenetic studies of mosquito species.

The mitochondrial genomes of Culex tritaeniorhynchus and Culex pipiens pallens (Diptera: Culicidae) and comparison analysis with two other Culex species.

BACKGROUND: Culex tritaeniorhynchus and Culex pipiens pallens are the major vectors of the Japanese encephalitis virus and Wuchereria bancrofti, the causative agent of filariasis. The knowledge of mitochondrial genomes has been widely useful for the studies on molecular evolution, phylogenetics and population genetics. METHODS: In this study, we sequenced and annotated the mitochondrial (mt) genomes of Cx. tritaeniorhynchus and Cx. p. pallens, and performed a comparative analysis including four known mt genomes of species of the subgenus Culex (Culex). The phylogenetic relationships of Cx. tritaeniorhynchus, Cx. p. pallens and four known Culex mt genome sequences were reconstructed by maximum likelihood based on concatenated protein-coding gene sequences. RESULTS: Culex tritaeniorhynchus and Cx. p. pallens mt genomes are 14,844 bp and 15,617 bp long, both consists of 13 PCGs, 22 tRNAs, 2 rRNAs and 1 CR (not sequenced for Cx. tritaeniorhynchus). The initiation and termination codons of PCGs are ATN and TAA, respectively, except for COI starting with TCG, and COI and COII terminated with T. tRNAs have the typical clover-leaf secondary structures except for trnS ((AGN)) that is lacking the DHU stem. 16S rRNA and 12S rRNA secondary structures were drawn for the first time for mosquito mt genomes. The control region of Cx. p. pallens mt genome is 747 bp long and with four tandem repeat structures. Phylogenetic analyses demonstrated that the mt genome of Cx. tritaeniorhynchus was significantly separated from the remaining five mt genomes of Culex spp. Culex p. pipiens, Cx. p. pallens and Cx. p. quinquefasciatus formed a monophyletic clade with Cx. p. quinquefasciatus linked in the middle of the clade, and Cx. p. pallens should have the same taxonomic level as Culex p. pipiens and Cx. p. quinquefasciatus. CONCLUSIONS: The mt genomes of Cx. tritaeniorhynchus and Cx. p. pallens share the same gene composition and order with those of two other Culex species. Culex p. pallens of the Pipiens complex should have the same taxonomic level as Culex p. pipiens and Cx. p. quinquefasciatus investigated. We enriched the Culex mt genome data and provided a reference basis for further Culex mt genome sequencing and analyses.