MIR600HG suppresses metastasis and enhances oxaliplatin chemosensitivity by targeting ALDH1A3 in colorectal cancer.

Metastasis and chemoresistance indicate a poor prognosis in colorectal cancer (CRC) patients. However, the mechanisms that lead to the development of chemoresistance and metastasis in CRC remain unclear. We combined clinical and experimental studies to determine the role of MIR600HG in CRC metastasis and chemoresistance. The statistical analysis was performed using GraphPad Prism software, version 8.0. We detected down-regulated expression of long non-coding RNA (lncRNA) MIR600HG in CRC specimens and cell lines compared with normal controls, and the expression level of MIR600HG was inversely correlated with the overall survival of CRC patients. The inhibition of MIR600HG stimulated CRC cell metastasis and chemoresistance. In addition, our data showed that the inhibition of MIR600HG stimulated CRC stemness, while the overexpression of MIR600HG suppressed stemness. Importantly, our animal experiments showed that MIR600HG inhibited tumour formation and that the combination of MIR600HG inhibition and oxaliplatin (Oxa) treatment significantly inhibited tumour growth compared with that with either intervention alone. Furthermore, we demonstrated that MIR600HG exerts its anticancer role by targeting ALDH1A3 in CRC. Our data suggest that MIR600HG functions as a tumour suppressor and that the overexpression of MIR600HG inhibits tumour invasion and enhances chemosensitivity, providing a new strategy for CRC treatment.

Yao Y ，Li N 《-》

Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer.

Liu T ，Zhang X ，Du L ，Wang Y ，Liu X ，Tian H ，Wang L ，Li P ，Zhao Y ，Duan W ，Xie Y ，Sun Z ，Wang C ... -  《Molecular Cancer》

MicroRNA‑487b‑3p inhibits osteosarcoma chemoresistance and metastasis by targeting ALDH1A3.

Cheng M ，Duan PG ，Gao ZZ ，Dai M ... -  《-》

circHIPK3 promotes oxaliplatin-resistance in colorectal cancer through autophagy by sponging miR-637.

Resistance to oxaliplatin-based chemotherapy is a major cause of recurrence in colorectal cancer (CRC) patients. There is increasing evidence indicating that circHIPK3 is involved in the development and progression of tumours. However, little is known about the potential role of circHIPK3 in CRC chemotherapy and its molecular mechanisms in chemoresistance also remain unclear. Quantitative real-time PCR was performed to detect circHIPK3 expression in tissues of 2 cohorts of CRC patients who received oxaliplatin-based chemotherapy. The chemoresistant effects of circHIPK3 were assessed by cell viability, apoptosis, and autophagy assays. The relationship between circHIPK3, miR-637, and STAT3 mRNA was confirmed by biotinylated RNA pull-down, luciferase reporter, and western blot assays. In the pilot study, increased circHIPK3 expression was observed in chemoresistant CRC patients. Functional assays showed that circHIPK3 promoted oxaliplatin resistance, which was dependent on inhibition of autophagy. Mechanistically, circHIPK3 sponged miR-637 to promote STAT3 expression, thereby activating the downstream Bcl-2/beclin1 signalling pathway. A clinical cohort study showed that circHIPK3 was upregulated in tissues from recurrent CRC patients and correlated with tumour size, regional lymph node metastasis, distant metastasis, and survival. circHIPK3 functions as a chemoresistant gene in CRC cells by targeting the miR-637/STAT3/Bcl-2/beclin1 axis and might be a prognostic predictor for CRC patients who receive oxaliplatin-based chemotherapy. National Natural Science Foundation of China (81301506), Shandong Medical and Health Technology Development Project(2018WSB20002), Shandong Key Research and Development Program (2016GSF201122), Natural Science Foundation of Shandong Province (ZR2017MH044), and Jinan Science and Technology Development Plan(201805084, 201805003).

Zhang Y ，Li C ，Liu X ，Wang Y ，Zhao R ，Yang Y ，Zheng X ，Zhang Y ，Zhang X ... -  《EBioMedicine》

LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance.

Hu HF ，Han L ，Fu JY ，He X ，Tan JF ，Chen QP ，Han JR ，He QY ... -  《Theranostics》