Increased α-tubulin1b Expression Indicates Poor Prognosis and Resistance to Chemotherapy in Hepatocellular Carcinoma

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2013 Apr 30

PMID 23625295

Citations 37

Authors

Cuihua Lu

Jing Zhang

Song He

Chunhua Wan

Aidong Shan

Yingying Wang

Litao Yu

Guoliang Liu

Ken Chen

Jing Shi

Yixin Zhang

Runzhou Ni

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. It is important to understand molecular mechanisms of HCC progression and to develop clinically useful biomarkers for the disease.

Aim: We aimed to investigate the possible involvement of α-tubulin1b (TUBA1B) in HCC pathology.

Methods: Tissue specimens were obtained from 114 HCC patients during hepatectomy. Immunohistochemistry and western blot analysis were used to detect TUBA1B expression in HCC tissues and cell lines. TUBA1B was knocked down in HCC cells by siRNA transfection. CCK-8 assay and flow cytometry were applied to determine cell proliferation and cell cycle progression, respectively. The efficacy of paclitaxel chemotherapy was evaluated by plate colony formation assay.

Results: TUBA1B was higher expressed in HCC tumor tissues than in adjacent nontumor tissues. TUBA1B and Ki-67 expressions were positively related to each other, and both their expressions were significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that TUBA1B was a significant predictor for overall survival of HCC patients. TUBA1B expression was increased in HCC cells during the G1- to S-phase transition. TUBA1B knockout in HCC cells inhibited cell proliferation, and attenuated resistance to paclitaxel.

Conclusions: Our results indicated that TUBA1B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increased TUBA1B expression was associated with poor overall survival and resistance to paclitaxel of HCC patients.

Citing Articles

TUBA1B as a novel prognostic biomarker correlated with immunosuppressive tumor microenvironment and immunotherapy response.

Qi J, Zhou M, Yang N, Ma H, He M, Wu G Front Pharmacol. 2025; 16:1517887.

PMID: 39968182 PMC: 11832512. DOI: 10.3389/fphar.2025.1517887.

Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.

Li D, Yang Z, Leng A, Zhang Q, Zhang X, Bian Y Mol Med. 2024; 30(1):119.

PMID: 39129004 PMC: 11318240. DOI: 10.1186/s10020-024-00892-x.

Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer.

Wang Y, Li Y, Jing Y, Yang Y, Wang H, Ismtula D Sci Rep. 2024; 14(1):8201.

PMID: 38589634 PMC: 11001892. DOI: 10.1038/s41598-024-58982-z.

TUBA1C is a potential new prognostic biomarker and promotes bladder urothelial carcinoma progression by regulating the cell cycle.

Jiang Y, Zhu C, Huang H, Huang G, Fu B, Xi X BMC Cancer. 2023; 23(1):716.

PMID: 37528357 PMC: 10391756. DOI: 10.1186/s12885-023-11209-2.

Tubulin Alpha-1b as a Potential Biomarker for Lung Adenocarcinoma Diagnosis and Prognosis.

Pang X, Du H, Nie F, Yang X, Xu Y Technol Cancer Res Treat. 2023; 22:15330338231178391.

PMID: 37489256 PMC: 10369087. DOI: 10.1177/15330338231178391.

References

Cho E, Whipple R, Matrone M, Balzer E, Martin S . Delocalization of gamma-tubulin due to increased solubility in human breast cancer cell lines. Cancer Biol Ther. 2009; 9(1):66-76. PMC: 4073665. DOI: 10.4161/cbt.9.1.10451. View

Blenk S, Engelmann J, Pinkert S, Weniger M, Schultz J, Rosenwald A . Explorative data analysis of MCL reveals gene expression networks implicated in survival and prognosis supported by explorative CGH analysis. BMC Cancer. 2008; 8:106. PMC: 2442114. DOI: 10.1186/1471-2407-8-106. View

Mann C, Neal C, Garcea G, Manson M, Dennison A, Berry D . Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer. 2007; 43(6):979-92. DOI: 10.1016/j.ejca.2007.01.004. View

Hage-Sleiman R, Herveau S, Matera E, Laurier J, Dumontet C . Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells. BMC Cancer. 2010; 10:135. PMC: 2859754. DOI: 10.1186/1471-2407-10-135. View

Kaibori M, Tanigawa N, Kariya S, Ikeda H, Nakahashi Y, Hirohara J . A prospective randomized controlled trial of preoperative whole-liver chemolipiodolization for hepatocellular carcinoma. Dig Dis Sci. 2012; 57(5):1404-12. DOI: 10.1007/s10620-012-2029-3. View

Kim N, Park E, Kim Y, Moon S, Lee S, Ahn S . Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents. Bioorg Med Chem. 2010; 18(19):7092-100. DOI: 10.1016/j.bmc.2010.07.072. View

Kaira K, Serizawa M, Koh Y, Miura S, Kaira R, Abe M . Expression of excision repair cross-complementation group 1, breast cancer susceptibility 1, and β III-tubulin in thymic epithelial tumors. J Thorac Oncol. 2011; 6(3):606-13. DOI: 10.1097/JTO.0b013e31820b9b35. View

Ohishi Y, Oda Y, Basaki Y, Kobayashi H, Wake N, Kuwano M . Expression of beta-tubulin isotypes in human primary ovarian carcinoma. Gynecol Oncol. 2007; 105(3):586-92. DOI: 10.1016/j.ygyno.2007.01.044. View

Takano T, Hasegawa Y, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K . Overexpression of kalpha1 tubulin mRNA in thyroid anaplastic carcinoma. Cancer Lett. 2001; 168(1):51-5. DOI: 10.1016/s0304-3835(01)00509-2. View

10.

Mechetner E, Kyshtoobayeva A, Zonis S, Kim H, Stroup R, Garcia R . Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res. 1998; 4(2):389-98. View

11.

Ke Q, Ji J, Cheng C, Zhang Y, Lu M, Wang Y . Expression and prognostic role of Spy1 as a novel cell cycle protein in hepatocellular carcinoma. Exp Mol Pathol. 2009; 87(3):167-72. DOI: 10.1016/j.yexmp.2009.07.011. View

12.

Hari M, Wang Y, Veeraraghavan S, Cabral F . Mutations in alpha- and beta-tubulin that stabilize microtubules and confer resistance to colcemid and vinblastine. Mol Cancer Ther. 2003; 2(7):597-605. View

13.

Schibler M, Cabral F . Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha- and beta-tubulin. J Cell Biol. 1986; 102(4):1522-31. PMC: 2114175. DOI: 10.1083/jcb.102.4.1522. View

14.

Wang Y, Yang S, Ni Q, He S, Zhao Y, Yuan Q . Overexpression of forkhead box J2 can decrease the migration of breast cancer cells. J Cell Biochem. 2012; 113(8):2729-37. DOI: 10.1002/jcb.24146. View

15.

Cho S, Kim Y, Surh Y, Kim B, Lee S . Ibulocydine is a novel prodrug Cdk inhibitor that effectively induces apoptosis in hepatocellular carcinoma cells. J Biol Chem. 2011; 286(22):19662-71. PMC: 3103345. DOI: 10.1074/jbc.M110.209551. View

16.

Kohno K, Kikuchi J, Sato S, Takano H, Saburi Y, Asoh K . Vincristine-resistant human cancer KB cell line and increased expression of multidrug-resistance gene. Jpn J Cancer Res. 1988; 79(11):1238-46. PMC: 5917651. DOI: 10.1111/j.1349-7006.1988.tb01550.x. View

17.

Simonetti R, Liberati A, Angiolini C, Pagliaro L . Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol. 1997; 8(2):117-36. DOI: 10.1023/a:1008285123736. View

18.

Cheung C, Wu S, Lee T, Chang C, Wu J, Hsieh H . Cancer cells acquire mitotic drug resistance properties through beta I-tubulin mutations and alterations in the expression of beta-tubulin isotypes. PLoS One. 2010; 5(9):e12564. PMC: 2933234. DOI: 10.1371/journal.pone.0012564. View

19.

Koh Y, Jang B, Han S, Kim T, Oh D, Lee S . Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer. J Thorac Oncol. 2010; 5(3):320-5. DOI: 10.1097/JTO.0b013e3181ce684f. View

20.

Nikas J, Boylan K, Skubitz A, Low W . Mathematical prognostic biomarker models for treatment response and survival in epithelial ovarian cancer. Cancer Inform. 2011; 10:233-47. PMC: 3201114. DOI: 10.4137/CIN.S8104. View