Search

Triple-negative breast cancer (TNBC) is the most common type of cancer among females worldwide and is associated with poor prognosis. Poly ADP-ribose polymerase-1 (PARP1) inhibitors are effective against TNBC with mutations in the breast cancer type 1 susceptibility protein (BRCA1) and/or BRCA2 genes; however, the development of resistance to PARP1 inhibitors limits their use. Thus, identifying strategies to overcome this resistance is urgently required. The aim of the present study was to investigate the potential function and mechanism of small interfering (si)RNA-MAPK4 (siMAPK4) in enhancing the efficacy of a PARP1 inhibitor and reducing the resistance. In the present study, data on the mRNA expression level of MAPK4 in normal breast tissues and TNBC tissues were obtained from The Cancer Genome Atlas database. The mRNA and protein expression levels of MAPK4 in normal breast cells and TNBC cells were analyzed using reverse transcription-quantitative PCR and western blotting, respectively. The phosphorylated (p) histone H2AX (γH2AX) protein expression was assessed via immunofluorescence. Cell Counting Kit-8, wound healing and TUNEL assays were used to determine the proliferative, migratory and apoptotic abilities of HCC1937 cells. MAPK4 was highly expressed in TNBC patient tissues and cell lines. Moreover, overexpression of MAPK4 could promote HCC1937 cell proliferation. Treatment of HCC1937 cells with the combination of siMAPK4 and a PARP1 inhibitor olaparib decreased their proliferation and migration and increased their apoptosis. The protein expression levels of the DNA repair-related proteins p-DNA-dependent protein kinase catalytic subunit (DNA-PK) and RAD51 recombinase (RAD51) were inhibited in the siMAPK4 and siMAPK4 + olaparib groups. However, the marker of a double-stranded break γH2AX showed increased protein expression in the siMAPK4 + olaparib group. As MAPK4 could phosphorylate AKT at threonine 308 (AKTT308), the current study restored p-AKTT308 using a constitutively active AKT plasmid (AKT-CA). p-DNA-PK and RAD51 showed high expression and γH2AX exhibited lower protein expression in the AKT-CA group. The present findings suggested that siMAPK4 can enhance the sensitivity of TNBC cells to PARP1 inhibitors.

The complete mitochondrial genomes of Harpago chiragra and Lambis lambis (Strombidae) were determined with the size of 15,460 bp and 15,481 bp, respectively, and both sequences contained 13 protein-coding genes, 22 tRNAs, and two rRNAs. H. chiragra and L. lambis have similar mitochondrial features, corresponding to typical gastropod mitochondrial genomes, such as the conserved gene order, a high A + T content (66.22% for H. chiragra and 66.10% for L. lambis), and preference for A + T-rich codons. The start or termination codon of same protein-coding gene in H. chiragra was consistent with that in L. lambis, except for the termination codon of cox1 gene (TAG for H. chiragra and TAA for L. lambis) and the start codon of nad4 (GTG for H. chiragra and ATG for L. lambis). Pairwise sequence alignments detected different degrees of variations in H. chiragra and L. lambis mitochondrial genomes; and the two species had lower levels of genetic distance (0.202 for nucleotide sequence) and closest relationships as compared to Strombus gigas and Oncomelania hupensis. The 13 partitioned nucleotide sequences of protein coding genes of H. chiragra and L. lambis were aligned with representatives of the main lineages of gastropods and their phylogenetic relationships were inferred. H. chiragra and L. lambis share the same gene order as Littorinimorpha species, except Vermetoidea, which demonstrate a gene rearrangement in species. The reconstructed phylogeny supports three major clades within Littorinimorpha: 1) Stromboidea, Tonnoidea, Littorinoidea, and Naticoidea, 2) Rissooidea and Truncatelloidea, and 3) Vermetoidea. In addition, a relaxed molecular clock calibrated with fossils dated the diversification of Strombidae near 112 (44–206) Mya and a possible radiation is detected to occur between 45–75 Mya, providing implications to understand the Cenozoic replacement event (65–135 Mya) of Aporrhaidae by Strombidae.

Background Aberrant methylation is common during the early stage of cancer development. This study was designed to investigate DNA methylation as biomarker for breast cancer. Methods Public database analysis and methylation-specific whole-gene sequencing were conducted to identify methylated biomarkers that would enable early non-invasive diagnosis of breast cancer. Firstly, the data was obtained from the TCGA Database and the Blueprint Epigenome Database. Secondly, methylation-specific whole-gene sequencing was conducted in 10 female patients with early-stage breast cancer and 10 healthy female volunteers from Nanfang Hospital of Southern Medical University between March 2018 and July 2018. Thirdly, the R language was used for data analysis, and KEGG and DAVID online tool was used for annotations. Results We found that methylation levels at 13 cytosine-phosphate-guanine (CpG) sites (cg04066177, cg04281344, cg05995576, cg06221609, cg08642731, cg11388802, cg12665414, cg14557216, cg19404723, cg19457909, cg24570211, cg25818763, and cg26215982) in the malignant tissue DNA were highly comparable to those of circulating cell-free DNA (cfDNA) of breast cancer patients, but were significantly different from those of normal tissue DNA, cfDNA of healthy women, and leukocyte DNA. In addition, three CpG sites (cg04281344, cg24570211, and cg26215982) were confirmed in clinical research, which showed that the sensitivity and specificity of these CpGs as biomarkers for breast cancer were 69.4-83.7% and 85.7-88.6%, respectively. Conclusions New biomarkers were identified and confirmed for breast cancer by comparing the methylation of tumour tissues, leukocytes, and non-plasma DNA.

The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR‑409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR‑409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR‑409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR‑409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR‑409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR‑409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR‑409-3p. In a xenograft model using nude mice, we examined the effects of miR‑409-3p on tumor growth during chemotherapy. miR‑409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

Rochia nilotica is a common marine gastropod species in family Tegulidae. At present, less molecular information of genus Rochia was reported. In the present study, we first determined the complete...

The complete mitochondrial genome of Temnopleurus hardwickii was sequenced using long-PCR and primer walking methods. The complete mitochondrial genome is a 15,696 bp circular molecule which contains 22 tRNAs, 2 rRNAs, 13 protein-coding genes as well as a non-coding control region as in other urchin. The genome was composed of 32.9% A, 29.3% T, 21.4% C and 16.4% G, showing a slight AT bias (62.3%). The control region is 156 bp. Twelve of the 13 mitochondrial protein-coding genes use ATG as their start codon while the ATP8 gene starts with GTG. All the 13 mitochondrial protein-coding genes use TAG or TAA as their complete stop codon.

The complete mitochondrial genome of Diadema setosum was sequenced by using long-PCR and primer walking methods. The complete mitochondrial genome is a 15,708 bp circular molecule, which contains 22 tRNAs, 2 rRNAs, and 13 protein-coding genes as well as a non-coding control region as in other urchin. The genome was composed of 27.5% A, 30.7% T, 24.3% C, and 17.5% G. The control region is 133 bp. Twelve of the 13 mitochondrial protein-coding genes use ATG as their start codon while the ATP8 gene starts with GTG. Six of the 13 mitochondrial protein-coding genes use TAA as their complete stop codon while seven of them use TAG as their complete stop codon.