mRNA vaccine in cancer therapy: Current advance and future outlook.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisition. In this review, we elaborated on the development of cancer vaccines and mRNA cancer vaccines, as well as the potential biological mechanisms of mRNA cancer vaccines and the latest progress in various tumour treatments, and discussed the challenges and future directions for the field.

A high level of the long non-coding RNA MCF2L-AS1 is associated with poor prognosis in breast cancer and MCF2L-AS1 activates YAP transcriptional activity to enhance breast cancer proliferation and metastasis.

Breast cancer (BC) is one of the most prevalent gynecologic malignant tumors with a poor prognosis and the second leading cause of cancer-related deaths in women worldwide. In recent years, it has been shown that long non-coding RNA (lncRNA) plays an important role in the development of breast cancer (BC). An antisense lncRNA from the MCF2 cell line (MCF2L-AS1) has been discovered recently and has been shown to function in a variety of malignancies. However, its function as a regulator of BC development has yet to be determined. Herein, the bioinformatics study analysis showed that MCF2L-AS1 was frequently highly expressed in BC tumors, and this overexpression was associated with worse patient outcomes. BC cells' proliferation, migration, and invasion are inhibited when MCF2L-AS1 is silenced, whereas the inverse is evident when MCF2L-AS1 is overexpressed. It was also observed that MCF2L-AS1 knockdown decreased carcinogenesis in xenograft tumor models. Furthermore, we discovered that MCF2L-AS1 could bind to and improve the transcription activity of the yes-associated protein (YAP). However, following YAP knockdown, this lncRNA's ability to drive BC malignancy was considerably reduced. In conclusion, MCF2L-AS1 may represent a potential predictive biomarker in BC patients, as well as a key regulator of BC cell proliferation. It works through positive feedback processes involving direct YAP binding and subsequent modulation of intracellular gene expression. Our findings add to our understanding of MCF2L-AS1 regulation and its potential as a therapeutic target in patients with this fatal cancer type.

Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in triple negative breast cancer.

Breast cancer is the leading cause of women death worldwide. Several long non-coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors during the progression of cancers. However, the role of taurine upregulated gene (TUG1) in mediating the chemotherapy sensitivity of triple negative breast cancer (TNBC) has not been studied yet. In TNBC patients, we observed a significant decrease of TUG1 in tumor tissues compared to the normal tissues. Similarly, TUG1 expression was significantly decreased in TNBC cell lines compared with normal breast epithelial cell line and cell lines of other subtypes of breast cancer. In MDA-MB-231 and BT549, cisplatin induced cell growth arrest was remarkably augmented by overexpression of TUG1 and was significantly reduced by TUG1 silencing. Moreover, very low concentration of cisplatin caused cell proliferation inhibition in TUG1-overexpressed-TNBC cells. In addition, we found that TUG1 negatively regulated miR-197 expression in the tested TNBC cell lines. Sponging of TUG1 to miR-197 was proved by a dual luciferase reporter assay. We further predicted and validated that nemo-like kinase (NLK), which was positively controlled by TUG1, was a target gene of miR-197. Via regulation of miR-197/NLK, TUG1 inactivated WNT signaling pathway and thus increasing chemotherapy sensitivity of TNBC cells. Analysis of TCGA database showed that higher expression of TUG1 was associated with better prognosis in breast cancer patients. Our current study drew a preliminary conclusion that TUG1 was involved in chemotherapy sensitivity in TNBC cells.

Role of deregulated microRNAs in breast cancer progression using FFPE tissue.

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation and miRNA expression profiling analysis. We found that miR-21, miR-200b/c, miR-141, and miR-183 were consistently up-regulated in ADH, DCIS and IDC compared to normal, while miR-557 was uniquely down-regulated in DCIS. Interestingly, the most significant miRNA deregulations occurred during the transition from normal to ADH. However, the data did not reveal a step-wise miRNA alteration among discrete steps along tumor progression, which is in accordance with previous reports of mRNA profiling of different stages of breast cancer. Furthermore, the expression of MSH2 and SMAD7, two important molecules involving TGF-ß pathway, was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells. In this study, we have not only identified a number of potential candidate miRNAs for breast cancer, but also found that deregulation of miRNA expression during breast tumorigenesis might be an early event since it occurred significantly during normal to ADH transition. Consequently, we have demonstrated the feasibility of miRNA expression profiling analysis using archived FFPE tissues, typically with rich clinical information, as a means of miRNA biomarker discovery.