Effect of PHLDA2 on proliferation, migration, invasion and apoptosis in hepatocellular carcinoma cells

doi:10.16098/j.issn.0529-1356.2020.03.014

Abstract

Abstract:

Objective To observe the expression of pleckstrin homology like domain family A member 2 (PHLDA2) in hepatocellular carcinoma (HCC) and investigate the effects of PHLDA2 on cell proliferation, migration, invasion and apoptosis. Methods To analyze the expression of PHLDA2 in 369 cases of HCC tissues and 160 cases of adjacent normal tissues and the effect of PHLDA2 expression on overall survival rate of HCC patients by gene expression profiling interactive analysis (GEPIA) online database. Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assay. Invasion and migration were detected by Transwell assay. The percentage of apoptosis was measured by flow cytometry. The levels of Bax and cleaved Caspase-3 were measured by Western blotting. Results The expression of PHLDA2 was upregulated in HCC, and high expression of PHLDA2 reduced the overall survival of HCC patients. Low-expression of PHLDA2 inhibited proliferation, invasion and migration, and increased apoptosis of HCC cells. Conclusion PHLDA2 promotes the occurrence and development and may act as a tumor promoter in HCC.

Key words: PHLDA2, Hepatocellular carcinoma, Proliferation, Colony formation, Flow cytometry

CLC Number:

R735.7

MA Zhan JIANG Zhong-xiang JIANG Zheng. Effect of PHLDA2 on proliferation, migration, invasion and apoptosis in hepatocellular carcinoma cells[J]. Acta Anatomica Sinica, 2020, 51(3): 398-404.

References

［1］ El-Serag HB. Hepatocellular carcinoma［J］. N Engl J Med, 2011, 365(12): 1118-1127.

［2］ Villanueva A, Llovet JM. Liver cancer in 2013: Mutational landscape of HCC-the end of the beginning［J］. Nat Rev Clin Oncol, 2014, 11(2): 73-74.

［3］ Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in Globocan 2012［J］. Int J Cancer, 2015, 136(5): E359-E386.

［4］ Baran Y, Subramaniam M, Biton A, et al. The landscape of genomic imprinting across diverse adult human tissues［J］. Genome Res, 2015, 25(7): 927-936.

［5］ Mohindra V, Tripathi RK, Yadav P, et al. Hypoxia influences expression profile of pleckstrin homology-like domain, family A, member 2 in Indian catfish, Clarias batrachus (Linnaeus, 1758): a new candidate gene for hypoxia tolerance in fish［J］. J Biosci, 2014, 39(3): 433-442.

［6］ Lv Y, Dai H, Yan G, et al. Downregulation of tumor suppressing STF cDNA 3 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by the Wnt/GSK-3β/β-catenin/Snail signaling pathway［J］. Cancer Letters, 2016, 373(2): 164-173.

［7］ Wang X, He H, Zhang K, et al. The expression of TSSC3 and its prognostic value in patients with osteosarcoma［J］. Biomed Pharmacother, 2016, 79: 23-26.

［8］ Moon H, Oh K, Lee J, et al. Prognostic and functional importance of the engraftment-associated genes in the patient-derived xenograft models of triple-negative breast cancers［J］. Breast Cancer Res Treat, 2015, 154(1): 13-22.

［9］ Idichi T, Seki N, Kurahara H, et al. Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation［J］. Cancer Sci, 2018, 109(6): 2013-2026.

［10］ Yan GN, Tang XF, Zhang XC, et al. TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway［J］. Oncotarget, 2017, 8(49): 85628-85641.

［11］ Dai J, Lin X, Guo MY, et al. Effect and molecular mechanism of trefoil factor family 3 on the cell cycle of thyroid papillary carcinoma cell［J］. Acta Anatomica Sinica, 2019, 50(2): 211-219.(in Chinese)

代金，林旭，郭梦姚，等. 三叶因子3对甲状腺乳头状癌细胞周期的影响及机制［J］. 解剖学报, 2019, 50(2): 211-219.

［12］ Xue ShH, Lu ZhY, Zhang TCh, et al. Expression and mechanism of micro RNA-940 in breast cancer［J］. Acta Anatomica Sinica, 2019, 50(1): 56-62.(in Chinese)

薛世航，陆振一，张同成，等. MicroRNA-940在乳腺癌中的表达变化及作用机制［J］. 解剖学报, 2019, 50(1): 56-62.

［13］ Goldgar DE, Easton DF, Cannon-Albright LA, et al. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands［J］. J Natl Cancer Inst, 1994, 86(21): 1600-1608.

［14］ Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk［J］. J Natl Cancer Inst, 2000, 92(1): 61-68.

［15］ Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk［J］. Lancet Oncol, 2002, 3(9): 565-574.

［16］ Kolonel LN, Altshuler D, Henderson BE. The multiethnic cohort study: exploring genes, lifestyle and cancer risk［J］. Nat Rev Cancer, 2004, 4(7): 519-527.

［17］ Lu Z, Luo RZ, Lu Y, et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells［J］. J Clin Invest, 2008, 118(12): 3917-3929.

［18］ Fresno VJ, Casado E, de Castro J, et al. PI3K/Akt signalling pathway and cancer［J］. Cancer Treat Rev, 2004, 30(2): 193-204.

［19］ Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis［J］. Dev Cell, 2008, 14(6): 818-829.

［20］ Takao T, Asanoma K, Tsunematsu R, et al. The maternally expressed gene Tssc3 regulates the expression of MASH2 transcription factor in mouse trophoblast stem cells through the Akt-Sp1 signaling pathway［J］. J Biol Chem, 2012, 287(51): 42685-42694.

[1]	ZHAO Wei-ming LI Xiao YU Guo-ying WANG Gai-ping CHANG Cui-fang . Effect of serine protease inhibitor Kazaltype 1 on the proliferation of hepatocellular carcinoma cell and its mechanism [J]. Acta Anatomica Sinica, 2023, 54(6): 695-702.
[2]	YU Hua-jing WEI Lu-yang LIU Shan-shan GUAN Cheng-jian ZHANG Zhong-tao. Role and clinical significance of MLLT1 super elongation complex subunit in the occurrence and development of hepatocellular carcinoma [J]. Acta Anatomica Sinica, 2023, 54(4): 425-433.
[3]	. Expression and prognostic significance of targeting protein for xenopus kinesin-like protein 2 in hepatocellular carcinoma [J]. Acta Anatomica Sinica, 2023, 54(4): 434-444.
[4]	GUAN Cheng-jian YU Hua-jing ZHANG Xiao-dong RAO Quan ZHANG Wei-tao LIU Kun WU Hong-wei WANG Dong ZHANG Zhong-tao GUO Wei. Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods [J]. Acta Anatomica Sinica, 2022, 53(6): 744-753.
[5]	YAN Xiao-di XUE Qiang WANG Fei-ran GU Hong-mei TANG Chong LIU Rui-qi ZHOU You-lang LIU Xian-cheng. Molecular mechanism of microRNA-29a-3p targeting Serpinh1 regulating proliferation and invasion of human gastric cancer cell line BGC823 [J]. Acta Anatomica Sinica, 2022, 53(5): 607-612.
[6]	XIANG Li-chun JIANG Zhong-xiang JIANG Xiao-ye CHEN Xue-nuo JIANG Zheng. Differential expression and bioinformatics analysis of epsin3 in colorectal cancer [J]. Acta Anatomica Sinica, 2022, 53(4): 507-514.
[7]	WANG Shu YIN Lu LIU Hong-bin XU Jia-zhi ZHAO Ji-bo PAN Yun-zhi SUN Yu-rong. Imiquimod inhibiting the proliferation of gliocytoma U87 cells by down-regulating STAT3/nuclear factor-κB signal pathway [J]. Acta Anatomica Sinica, 2022, 53(3): 323-329.
[8]	WANG Yang ZHAO Bao-sheng LI Chao-hong LIU Yu-zhen. Effects of acetyl-CoA carboxylase 1 on proliferation, migration and invasion of glioma cell line U87 [J]. Acta Anatomica Sinica, 2022, 53(3): 317-322.
[9]	GUO Jian-lin WANG Xue-qing XU Cun-shuan. Advances in biological functions of miR-429 [J]. Acta Anatomica Sinica, 2022, 53(2): 266-272.
[10]	YAN Ting ZHAO Ji-kai WANG En-hua. MEX3A promotes proliferation and migration of colorectal cancer cells via PI3K/Akt signaling pathway [J]. Acta Anatomica Sinica, 2022, 53(2): 196-202.
[11]	JIANG Hong HUANG Yan-li XING Hui WANG Li-ming GUO Hong . Effects of miR-515-5p on the proliferation and metastasis of ovarian cancer cell A2780 by regulating the expression of chondroitin sulfate proteoglycan 4 and its mechanism [J]. Acta Anatomica Sinica, 2022, 53(1): 42-49.
[12]	ZHAO Ke-chang WANG Wei YANG Jin-yu FENG Peng-cai WU Shi-le. Effect of short hairpin RNA lentivirus-mediated silencing of pleomorphic adenoma gene like-2 on proliferation, migration and invasion of hepatocellular carcinoma cells [J]. Acta Anatomica Sinica, 2022, 53(1): 75-81.
[13]	HUANG Ke-ke QI Bo GU Cheng-wei HUO Shu-hua LIU Yu-zhen ZHAO Bao-sheng. Low expression S100 calcium ion binding protein A6 promoting the proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells#br# [J]. Acta Anatomica Sinica, 2021, 52(5): 737-743.
[14]	TAN Yu-jing DAI Zi-wei TANG Biao. Abnormal expression of glypican-3 and ubiquitin D in hepatocellular carcinoma and the associated interaction#br# [J]. Acta Anatomica Sinica, 2021, 52(5): 744-750.
[15]	LEI Lei LU Xuan YANG Jing-song YOU Yu-zhen MEI Yan. Histone deacetylase 3 inhibitor ameliorates hypoxia/reoxygenation injury in PC12 cells by reducing oxidative#br# [J]. Acta Anatomica Sinica, 2021, 52(5): 706-711.