Antitumor activity of SR splicing‐factor 5 knockdown by downregulating pyruvate kinase M2 in non–small cell lung cancer cells. Issue 10 (20th May 2019)

• Record Type: Journal Article
• Authors: Yan, Jiliang; Zhang, Dongya; Han, Yanjie; Wang, Zhongjie; Ma, Chunyan
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 10(2019)
• Page Start: 17303
• Page End: 17311
• Publication Date: 2019-05-20
• Subjects: apoptosis -- glycolysis -- NSCLC -- PKM2 -- proliferation -- SRSF5; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28992
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: SR splicing‐factors (SRSFs) play a vital role in carcinogenesis. SRSF5 was demonstrated to be upregulated in lung cancer and identified as a novel prognostic indicator for small‐cell lung cancer. However, the role of SRSF5 in the pathogenesis of non–small cell lung cancer (NSCLC) and the molecular mechanism involved are still undefined. The expression of SRSF5 in NSCLC cells was detected by quantitative real‐time polymerase chain reaction and Western blot analysis. The proliferation of cells was evaluated by cell counting kit‐8 and BrdU assays. Apoptosis was assessed by flow cytometry and Western blot analysis of apoptosis‐associated proteins including B‐cell lymphoma 2 (Bcl‐2), Bax, and cytochrome C (Cyt C). Glycolysis was detected by determining glucose consumption, lactate production, and pyruvate kinase M2 (PKM2) expression. We found that SRSF5 messenger RNA and protein levels were elevated in NSCLC cells. SRSF5 knockdown inhibited the proliferation and Ki67 expression in NSCLC cells. SRSF5 silencing increased the apoptotic rate, upregulated Bax and Cyt C, and decreased Bcl‐2 level in NSCLC cells. Moreover, Knockdown of SRSF5 repressed glycolysis in NSCLC cells via reducing PKM2 expression. Enhanced glycolysis by PKM2 overexpression attenuated the effects of SRSF5 silencing on NSCLC cell proliferation and apoptosis. Overall, knockdown of SRSF5 inhibited proliferative ability and induced apoptosis by suppressing PKM2 expression in NSCLC cells. Abstract : Knockdown of SR splicing‐factor 5 (SRSF5) inhibited proliferation and induced apoptosis by suppressing pyruvate kinase M2 (PKM2) expression in non–small cell lung cancer (NSCLC) cells. This contributes to a better understanding of the role of SRSF5 in NSCLC progression.