1. Academic Validation
  2. LINC00894 targets Annexin A2 to regulate oxaliplatin resistance in hepatocellular carcinoma: ANXA2 protein function

LINC00894 targets Annexin A2 to regulate oxaliplatin resistance in hepatocellular carcinoma: ANXA2 protein function

  • Int J Biol Macromol. 2024 Nov;281(Pt 3):136538. doi: 10.1016/j.ijbiomac.2024.136538.
Junling Huang 1 Jiajie Lin 2 Tengmeng Zhong 3 Zongshuai Qin 4 Guangzhi Li 5 Tingzhuang Yi 6 Xianzhe Lu 7 Yueqiu Qin 8
Affiliations

Affiliations

  • 1 The First Clinical Medical College of Jinan University, Guangzhou, Guangdong 530632, China; Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Province, China; Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Baise, Guangxi 533000, China.
  • 2 The First Clinical Medical College of Jinan University, Guangzhou, Guangdong 530632, China; Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Baise, Guangxi 533000, China; Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Guangxi Zhuang Autonomous Region Engineering Research Center for Biomaterials in Bone and Joint Degenerative Diseases, Baise, Guangxi 533000, China.
  • 3 Department of Hepatobiliary Surgery, Baise People's Hospital, Baise, 533000, Guangxi Province, China.
  • 4 Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Province, China.
  • 5 Department of General practice, Affiliated Hospital of Youjiang Medical University for Nationalities, No.18 Zhongshan 2nd Road, Baise 533000, Guangxi Province, China.
  • 6 Department of Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi Province, China.
  • 7 The First Clinical Medical College of Jinan University, Guangzhou, Guangdong 530632, China; Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Baise, Guangxi 533000, China; Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China; Guangxi Zhuang Autonomous Region Engineering Research Center for Biomaterials in Bone and Joint Degenerative Diseases, Baise, Guangxi 533000, China. Electronic address: 17707765677@163.com.
  • 8 Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Province, China. Electronic address: qinyueqiu@ymun.edu.cn.
Abstract

To investigate the role of LINC00894 in oxaliplatin chemoresistance of hepatocellular carcinoma (HCC) and its mechanisms. The oxaliplatin-resistant HCC cell lines were established. IC50 of oxaliplatin was calculated by CCK-8 assay. Cell viability was detected using clonal formation experiment, while cell Apoptosis was accessed by flow cytometry. RNA binding protein immunoprecipitation and RNA pull-down were performed to explore the interaction of LINC00894 and AnxA2. The expressions of RNA and protein were tested by qRT-PCR and western blot respectively. Tumor xenograft was performed to detect the effect of LINC00894 in vivo. The expression of ki67 was evaluated by immunohistochemistry staining. LINC00894 was overexpressed in HCC cells resistant to oxaliplatin. Elevated LINC00894 promoted HCC cells resistance to oxaliplatin, whereas silence of LINC00894 improved HCC sensitivity to oxaliplatin. LINC00894 could bind to the AnxA2 protein, enhanced the stability of the AnxA2 protein and reduced its ubiquitination. Furthermore, LINC00894 modulated HCC resistance to oxaliplatin both in vitro and in vivo by targeting the AnxA2 protein.LINC00894 enhanced the stability of AnxA2 protein and attenuated its ubiquitination by interacting with it, thereby promoting oxaliplatin resistance in HCC. Our findings contributed to understanding the role of these mechanisms in the process of oxaliplatin resistance in HCC.

Keywords

Annexin A2; Drug resistance; Hepatocellular carcinoma; LINC00894; Oxaliplatin.

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