Promotion of tumorigenesis by miR-1260b-targeting CASP8: Potential diagnostic and prognostic marker for breast cancer.
Sunyoung ParkJungho KimYoonjung ChoSungwoo AhnGeehyuk KimDasom HwangYunhee ChangSunmok HaYeonim ChoiMin Ho LeeHyunju HanSunghyun KimSeung-Il KimHyeyoung LeePublished in: Cancer science (2022)
MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.
Keyphrases
- induced apoptosis
- neoadjuvant chemotherapy
- endoplasmic reticulum stress
- poor prognosis
- lymph node
- locally advanced
- cell cycle arrest
- oxidative stress
- early stage
- breast cancer cells
- signaling pathway
- human health
- squamous cell carcinoma
- cell death
- binding protein
- radiation therapy
- long non coding rna
- gene expression
- rectal cancer
- pi k akt
- risk assessment
- clinical trial
- dna methylation
- drug delivery
- cancer therapy
- single cell
- copy number
- childhood cancer