No abstract

It is commonly accepted that cellular protein levels are primarily determined by mRNA levels. However, discordance between protein and mRNA expression has been implicated in many pathologic conditions including oncogenesis. The mechanisms involved in this discordance are complicated and far from understood. In this study, it was observed that the expression levels of poly(C) binding protein 2 (PCBP2) mRNA and protein were diametric in breast normal and cancer cell lines, paraffin-embedded and fresh tissue specimens, consistent with data from The Cancer Genome Atlas and the Clinical Proteomic Tumor Analysis Consortium. Moreover, PCBP2 protein expression was significantly associated with disease progression and poor outcome in patients with breast cancer. Depletion of PCBP2 protein inhibited cell proliferation, colony formation, migration, invasion, and in vivo tumor growth and metastasis. Forced expression of PCBP2 exhibited the opposite effect. Mechanistically, it was demonstrated that PCBP2 3′ untranslated region (3′UTR) was subject to alternative splicing and polyadenylation (APA) in breast cancer tissues and cell lines. Non-full-length 3′UTR PCBP2 transcripts yielded more protein than the full-length 3′UTR transcripts and enhanced the oncogenic and metastatic capacities of human breast cancer cells. Furthermore, UFD1 and NT5E were identified as genes downstream of PCBP2. PCBP2 promoted oncogenicity of breast cancer cells via upregulation of the expression of UFD1 and NT5E by direct binding to their 3′UTR-B portions. Implications: Findings demonstrate that APA of PCBP2 3′UTR contributes to its increased expression with subsequent promotion of breast cancer progression by regulating UFD1 and NT5E. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/19/1/86/F1.large.jpg.

Resistance to chemotherapy remains a major obstacle to the successful treatment of breast cancer. More than 80% of patients who receive neoadjuvant chemotherapy (NAC) do not achieve a pathological complete response. In this study, we report a novel p62 mRNA isoform with a short 3′-UTR (p62-SU, 662-nt) that is associated with chemoresistance in breast cancer cells and tissue specimens. The p62 mRNA isoform was identified by RNA sequencing with qRT-PCR, 3′-RACE, and northern blot analysis. In vitro and in vivo, ectopic expression of p62-SU promoted breast cancer cell proliferation, migration, invasion, and chemoresistance compared with the p62 mRNA isoform with a full-length 3′-UTR (p62-LU, 1,485-nt). Mechanistically, CPSF1 modulated the 3′-UTR of p62 through alternative polyadenylation. In addition, p62-SU escaped miR-124-3p-mediated repression and upregulated p62-SU protein expression, thereby inducing p62-dependent chemoresistance. These data suggest that a CPSF1-p62-miR-124-3p signaling axis is responsible for reduced sensitivity of breast cancer to chemotherapy.

Background: Both meta-analyses and systematic reviews were used to assess the relationship between purinergic receptor P2X ligand-gated ion channel 7 (P2RX7) rs3751143 polymorphism and the risk of cancer. Materials and methods: The data used in this research were collected from Google Scholar, Web of Science, CNKI, and Wan Fang Data databases. The final retrieval ended on 22 February 2019. The strength of correlation was assessed using odds ratios and 95% confidence intervals. Based on the heterogeneity test results, fixed-effect (Mantel–Haenszel) or random-effects (DerSimonian–Laird) models were selected to summarise the collective effects. Results: Eight separate studies containing 1462 cancer cases and 3037 controls were enrolled. Overall, there was no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, or recessive models. Conclusions: Our meta-analysis indicates that there is no significant association between P2RX7 rs3751143 polymorphism and the risk of cancer in the allelic, homozygous, heterozygous, dominant, and recessive models.

Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.