Abstract
Long non-coding RNA cancer susceptibility candidate 2 (lncRNA CASC2) is a tumor suppressor and has been proved to contribute to chemotherapy efficacy. However, the effect of CASC2 on cisplatin cytotoxicity in non-small cell lung cancer (NSCLC) is unclear. The present study aimed to investigate the role of CASC2 in regulating cisplatin cytotoxicity in NSCLC cells. Herein, we found that CASC2 was low-expressed, while miR-18a and miR-21 were over-expressed in NSCLC cell lines. CASC2 enhanced the inhibition effect of cisplatin on cell viability. Down-regulation of miR-18a and miR-21 exhibited the similar effect to CASC2 and mimics of miR-18a and miR-21 displayed the opposite effect to CASC2. MiR-18a and miR-21 were two targets of CASC2 in NSCLC. PTEN was found to be a target of miR-18a and miR-21 in NSCLC. CASC2 overexpression increased PTEN expression level and reduced the ratio of p-Akt/Akt. MiR-18a or miR-21 mimics attenuated the effect of CASC2 overexpression on the PTEN expression and ratio of p-Akt/Akt. The results suggested that CASC2 enhanced cisplatin-induced viability inhibition of NSCLC cells via PTEN/PI3K/Akt pathway through suppressing miR-18a and miR-21 expression.
Highlights
Lung cancer is one of the most common cancers and the leading cause of cancer-related mortality worldwide.[1]
We found that Cancer susceptibility candidate 2 (CASC2) enhanced cisplatin-induced viability inhibition of non-small cell lung cancer (NSCLC) cells by regulating the PTEN/PI3K/Akt pathway through down-regulation of miR-18a and miR-21
We investigated the role of CASC2 in regulating cisplatin cytotoxicity in NSCLC cells
Summary
Lung cancer is one of the most common cancers and the leading cause of cancer-related mortality worldwide.[1] There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).[2] It has been reported that NSCLC accounts for approximately 85% of all cases of lung cancer.[2] For early stages of NSCLC, the treatment is surgery, but for some locally advanced cancers and metastatic disease, the treatments are chemotherapy with concurrent radiation and palliative chemotherapy, respectively.[2] Cisplatin is an effective chemotherapeutic drug, which is usually used for the treatment of many cancers, the effect of cisplatin is diminished because of the drug resistance.[3] Cisplatin resistance has been found in the treatment of NSCLC.[4]
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