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Abstract
Mounting evidence highlights long non‐coding RNAs (lncRNAs) as crucial regulators in multiple types of biological processes and contributing to tumourigenesis. LINC01133, located in chromosome 1q23.2, was a recently identified novel lncRNA with a length of 1154nt. It was involved in the development of colorectal cancer and non‐small cell lung cancer. However, its clinical relevance, biological functions and potential molecular mechanism in breast cancer are still unclear. In this study, we found that the LINC01133 expression was significantly down‐regulated in breast cancer samples and was associated with progression and poor prognosis of breast cancer. Further experiments demonstrated that overexpression of LINC01133 inhibited invasion and metastasis in breast cancer both in vitro and in vivo. Mechanistic investigations revealed that LINC01133 repressed SOX4 expression by recruiting EZH2 to SOX4 promoter. Moreover, rescue experiments further confirmed that LINC01133 functional acted as an anti‐oncogene, at least partly, via repressing SOX4 in breast cancer. Taken together, these findings imply that LINC01133 could serve as a novel prognostic biomarker and potential therapeutic target for breast cancer.
Highlights
Breast cancer, originated from breast tissue, is the most commonly diagnosed malignant tumour and one of the leading causes of can‐ cer‐related death among women worldwide.[1,2] dramatic advancement has been made in the early diagnosis, and complex treatment such as surgical resection, radio‐chemotherapy, endo‐ crine therapy and immunotherapy, the prognosis of breast cancer patients is still poor due to high rate of lethal distant metastasis.[3]
Emerging evidence has indicated that Long non‐coding RNAs (lncRNAs) play piv‐ otal roles in breast cancer tumourigenesis and progression, such as ANCR, ROR, MEG3 and H19
ROR promoted oestrogen‐independent breast cancer cell growth and activation of MAPK/ERK pathway through regulating the ERK‐spe‐ cific phosphatase DUSP7.23 MEG3 inhibited breast cancer cell pro‐ liferation and invasion through regulating E‐cadherin expression by sponging to miR‐421.24 A feedback loop constituted of H19, let‐7 and LIN28 played an important role in breast cancer stem cells main‐ tenance.[25]
Summary
Breast cancer, originated from breast tissue, is the most commonly diagnosed malignant tumour and one of the leading causes of can‐ cer‐related death among women worldwide.[1,2] dramatic advancement has been made in the early diagnosis, and complex treatment such as surgical resection, radio‐chemotherapy, endo‐ crine therapy and immunotherapy, the prognosis of breast cancer patients is still poor due to high rate of lethal distant metastasis.[3]. It was reported that LINC01133 was involved in colorectal cancer and non‐small cell lung cancer.[13,14,15] its clinical relevance, biological functions and potential mechanism in breast cancer are still unclear. We found the LINC01133 expression significantly reduced in breast cancer tissues compared with paired adjacent normal breast tissues. The reduced LINC01133 expression was correlated with progres‐ sion and poor prognosis of breast cancer. We revealed that LINC01133 inhibited invasion and metastasis in breast cancer, partly through binding with EZH2 to mediate SOX4 transcriptional inhibition. A total of 74 paired breast cancer and adjacent normal breast tis‐ sues were collected from patients who were diagnosed with breast cancer according to histopathological evaluation and had received surgical resection at Shanghai Tongji Hospital.
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