Fatty acid ß-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway.

MicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid ß-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid ß-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.

LINC01816 promotes the migration, invasion and epithelial­mesenchymal transition of thyroid carcinoma cells by sponging miR­34c­5p and regulating CRABP2 expression levels.

Thyroid carcinoma (THCA) is a common type of endocrine system cancer and its current clinical treatment method is surgical resection. Long non­coding RNAs (lncRNAs) have been revealed to serve important roles in a variety of complex human diseases. Therefore, determining the association between lncRNAs and diseases may provide novel insight into disease­related lncRNAs, with the aim of improving disease treatments and diagnoses. Long intergenic non­protein coding RNA 1816 (LINC01816) was identified to be associated with the survival of patients with colorectal cancer using the IDHI­MIRW method. The present study aimed to investigate the role and molecular mechanism of LINC01816 in THCA. Analysis of datasets from The Cancer Genome Atlas database revealed that the upregulation of LINC01816 expression levels was associated with a variety of cancer types. Reverse transcription­quantitative PCR analysis demonstrated that compared with the normal thyroid tissues, the expression levels of LINC01816 were upregulated in THCA tissues. The results of wound healing and Transwell assays, and western blotting demonstrated that the overexpression of LINC01816 could strengthen the invasive and migratory abilities of THCA cells and enhance epithelial­mesenchymal transition progression. Analysis using the starBase website and dual­luciferase reporter assays identified that microRNA (miR)­34c­5p was a target of LINC01816. The overexpression of miR­34c­5p could inhibit the invasive and migratory abilities of THCA cells, in addition to inhibiting the cellular retinoic acid binding protein 2 (CRABP2) overexpression­induced effects on invasion, migration and EMT processes. In conclusion, the findings of the present study indicated that LINC01816 may be capable of sponging miR­34c­5p to upregulate CRABP2 expression levels, which subsequently promoted the invasion, migration and EMT of THCA cells. Therefore, targeting the LINC01816/miR­34c­5p/CRABP2 pathway may be an effective therapeutic approach for patients with THCA.

Long non-coding RNA signatures as predictors of prognosis in thyroid cancer: a narrative review.

Thyroid cancer (TC) is the most common endocrine malignancy, with high incidence rates in recent decades. Most TC cases have good prognoses, but a high risk of recurrence and metastases poses challenges, especially for patients with high-risk factors. Currently used prognostic markers for TC involve a combination of genetic factors and overexpressed proteins. Long non-coding RNAs (lncRNAs) regulate several integral biologic processes by playing key roles in the transcription of several downstream targets maintaining cellular behavior. Prior studies have revealed that lncRNAs promote tumor cell proliferation, invasion, metastasis, and angiogenesis, making them important targets for therapeutic intervention in cancer. While the exact molecular mechanisms underlying the role of lncRNAs in modulating TC progression and recurrence is still unclear, it is important to note that some lncRNAs are upregulated in certain cancers, while others are downregulated. In the present study, we review several key lncRNAs, their association with cancer progression, and the important roles they may play as tumor suppressors or tumor promoters in tumorigenesis. We discuss the potential mechanisms of lncRNA-mediated pathogenesis that can be targeted for the treatment of TC, the existing and potential benefits of using lncRNAs as diagnostic and prognostic measures for cancer detection, and tumor burden in patients.

WNT signaling pathway regulator-FRAT2 affects oncogenesis and prognosis of basal-like breast cancer.

BACKGROUND: Breast cancer is the most common malignant cancer in women worldwide and is one of the leading causes of cancer death. Basal-like breast cancer (BLBC) is an aggressive subtype of breast cancer for which targeted therapy has poor efficacy. Therefore, research into the molecular pathogenesis of BLBC is urgent for developing effective targeted therapeutic treatments. METHODS: We collected relevant data from the Cancer Genome Atlas (TCGA), including transcriptome, copy number variation, and survival data. We also gathered 30 pairs clinical samples of cancer tissues and non-cancerous tissues to perform Western Blotting (WB) to reveal the encoded protein expression levels. Besides, we knocked down frequently rearranged in advanced T-cell lymphomas 2 (FRAT2) expression in two representative cell lines (T47D and MDA-MB-231 cells). The cell cycle progression was analyzed, while the apoptosis experiments were also conducted to explore the molecular pathogenesis of FRAT2 in BLBC. RESULTS: The aberrant activation of the WNT pathway and highly expressed FRAT2 were specifically identified across the BLBC genome comparing to other types of tumor. In addition, FRAT2 expression was found to be positively associated with its copy number variations (P=9.126×10-23). For further investigation, we found the expression level of FRAT2 was related to the poor overall survival of BLBC patients (P=0.049). The results of WB revealed that FRTA2-encoded protein was overexpressed in BLBC tissues. Based on results in T47D and MDA-MB-231 cells in vitro, we found that knocking down FRAT2 can inhibit the proliferation of these two cell lines. In cell cycle progression experiments, cell cycle arrested in the G2/M phase. Meanwhile, increased apoptosis was also found in the shFRAT2 cell group in vitro. CONCLUSIONS: In BLBC basal-like breast cancer, we can assume that FRAT2 is a potential treatment target.