Highlights d NF1 is a GAP-independent estrogen receptor transcription co-repressor d Somatic NF1 loss causes tamoxifen/aromatase inhibitor resistance in ER + breast cancer d A MEK inhibitor plus a SERD is effective in NF1 -ER + PDX and cell line models
PurposeLong non-coding RNA taurine upregulated gene 1 (TUG1) is reported to be a vital regulator of the progression of various cancers. This study aimed to explore the exact roles and molecular mechanisms of TUG1 in osteosarcoma (OS) development.Materials and MethodsReal-time quantitative PCR was applied to detect the expressions of TUG1 and microRNA-132-3p (miR-132-3p) in OS tissues and cells. Western blot was performed to measure protein levels of sex determining region Y-box 4 (SOX4). Cell viability was assessed using XTT assay. Cell apoptosis was evaluated using flow cytometry and caspase-3 activity detection assays. Bioinformatics analysis and luciferase reporter experiments were employed to confirm relationships among TUG1, miR-132-3p, and SOX4.ResultsTUG1 was highly expressed in human OS tissues, OS cell lines, and primary OS cells. TUG1 knockdown hindered proliferation and induced apoptosis in human OS cell lines and primary OS cells. Moreover, TUG1 inhibited miR-132-3p expression by direct interaction, and introduction of miR-132-3p inhibitor partly abrogated the effect of TUG1 knockdown on the proliferation and apoptosis of OS cells. Furthermore, SOX4 was validated as a target of miR-132-3p. Further functional analyses revealed that miR-132-3p inhibited proliferation and induced apoptosis of OS cells, while this effect was greatly abated following SOX4 overexpression. Moreover, TUG1 knockdown suppressed proliferation and promoted apoptosis by upregulating miR-132-3p and downregulating SOX4 in primary OS cells.ConclusionTUG1 facilitated proliferation and suppressed apoptosis by regulating the miR-132-3p/SOX4 axis in human OS cell lines and primary OS cells. This finding provides a potential target for OS therapy.
Esophageal cancer is a common malignant tumor worldwide. Inherent and acquired drug resistance are the major challenges faced in anticancer chemotherapy. This study aimed to explore the effects of α-solanine in regards to the chemosensitivity of esophageal cancer cells. We found that α-solanine enhanced the sensitivity of EC9706 and KYSE30 cells to 5-flurouracil (5-FU) and cisplatin (Cis) by promoting drug-induced apoptosis. qRT-PCR and western blotting results showed that α-solanine treatment promoted miR-138 expression and decreased survivin expression in EC9706 and KYSE30 cells. α-solanine also enhanced the inhibitory effects of 5-Fu and Cis in EC9706 transplanted tumors in mouse models. Dual-Luciferase reporter assay results confirmed survivin as the direct target gene of miR-138. MiR-138 inhibited survivin expression in EC9706 and KYSE30 cells. And miR-138 mimic and si-survivin had similar effects with α-solanine in suppressing survivin expression and promoting cancer cell death. miR-138 inhibitor reversed the chemosensitivity-enhancing effect of α-solanine. In EC9706 and KYSE30 cells, survivin overexpression rescued the cancer cells from apoptosis caused by α-solanine and miR-138 mimic expression. From these findings, we conclude that α-solanine enhanced the chemosensitivity of esophageal cancer cells to chemotherapy via the miR-138/survivin pathway. This study provides insight into the molecular mechanism underlying the chemosensitivity-enhancing function of α-solanine and suggests a new chemotherapeutic strategy for esophageal cancer treatment.
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