title: SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.
abstract: SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell proliferation and migration. Additionally, SUN2 increases the sensitivity of lung cancer to cisplatin by inducing cell apoptosis. Mechanistically, we showed that SUN2 exerts its tumor suppressor functions by decreasing the expression of GLUT1 and LDHA to inhibit the Warburg effect. Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2.Taken together, our findings indicate that SUN2 is a key component in lung cancer progression by inhibiting the Warburg effect and that the novel SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer.
authors.affiliation: Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Xiao-bin
authors.initials: XB
authors.lastname: Lv
authors.affiliation: Department of Pharmacy, Jiangxi cancer Hospital, Nanchang, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of cardiothoracic surgery, the First Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Bentong
authors.initials: B
authors.lastname: Yu
authors.affiliation: Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Longxin
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Jiangxi cancer Hospital, Nanchang, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Jiangxi cancer Hospital, Nanchang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D037761:Sirtuins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C413025:SUN2 protein, human; C508544:SIRT5 protein, human; D037761:Sirtuins; D002945:Cisplatin