Abstract
Chemotherapy resistance frequently drives tumour progression. However, the underlying molecular mechanisms are poorly characterized. In this study, we explored miR-137's role in the chemosensitivity of lung cancer. We found that the expression level of miR-137 is down-regulated in the human lung cancer tissues and the resistant cells strains: A549/paclitaxel(A549/PTX) and A549/cisplatin (A549/CDDP) when compared with lung cancer A549 cells. Moreover, we found that overe-expression of miR-137 inhibited cell proliferation, migration, cell survival and arrest the cell cycle in G1 phase in A549/PTX and A549/CDDP. Furthermore, Repression of miR-137 significantly promoted cell growth, migration, cell survival and cell cycle G1/S transition in A549 cells. We further demonstrated that the tumor suppressive role of miR-137 was mediated by negatively regulating Nuclear casein kinase and cyclin-dependent kinase substrate1(NUCKS1) protein expression. Importantly, miR-137 inhibits A549/PTX, A549/CDDP growth and angiogenesis in vivo. Our study is the first to identify the tumor suppressive role of over-expressed miR-137 in chemosensitivity. Identification of a novel miRNA-mediated pathway that regulates chemosensitivity in lung cancer will facilitate the development of novel therapeutic strategies in the future.
Highlights
Lung cancer is the most frequent cause of cancerrelated death both in China and in many other countries
We tested the expression levels of miR-137 in 50 pairs of non-small cell lung cancer(NSCLC) tumor specimens and adjacent normal tissues, and found that miR-137 expression levels in tumor tissues were significantly lower than those controls (Figure 1A)
The expression levels of miR-137 were significantly lower in WHO stage III-IV NSCLC tissues than those in stage I and stage II, indicating that miR-137 expression was greatly down-regulated in late stages of lung cancer cancer tissues (Figure 1B)
Summary
Lung cancer is the most frequent cause of cancerrelated death both in China and in many other countries. Down-regulation of miR-137 expression in tumor tissues of human lung cancer patients We tested the expression levels of miR-137 in 50 pairs of non-small cell lung cancer(NSCLC) tumor specimens and adjacent normal tissues, and found that miR-137 expression levels in tumor tissues were significantly lower than those controls (Figure 1A).
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