RP11-738E22.3 promotes hepatocellular carcinoma progression by inhibiting autophagy and apoptosis via MAPK/ERK/mTOR pathway

  • Int J Biol Macromol. 2026 Jun:365:152371. doi: 10.1016/j.ijbiomac.2026.152371.
Yihong Chen  1 ,  Erya Hu  2 ,  Shiqi Tang  3 ,  Guangzu Cui  2 ,  Jiayao Ma  2 ,  Yin Li  2 ,  Haicong Liu  2 ,  Xin Zhou  2 ,  Qingping Peng  2 ,  Diya Tang  2 ,  Xinwen Wang  2 ,  Ying Han  1 ,  Changjing Cai  1 ,  Shan Zeng  1 ,  Hong Shen  4 ,  Binyuan Jiang  5
Affiliations
  • 1. Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, China.
  • 2. Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 3. Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China.
  • 4. Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, China. Electronic address: [email protected].
  • 5. Clinical Trials Office, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China; Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China. Electronic address: [email protected].
PMID: 42097423 DOI: 10.1016/j.ijbiomac.2026.152371
Abstract

Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor that poses a hazard to millions of people globally. Long intergenic noncoding RNAs (lincRNAs) have been recognized as key regulators influencing prognosis of HCC patients. However, their underlying mechanisms in HCC warrant further investigation. The role of the unreported lincRNA RP11-738E22.3 in HCC is still unknown. In this research, differentially expressed lincRNAs were identified using Arraystar long noncoding RNA (lncRNA) microarray Sequencing, and the expression levels of RP11-738E22.3 were measured by RT-qPCR and FISH. The impact of RP11-738E22.3 on HCC cell Autophagy, Apoptosis, xenograft tumor growth, and metastasis were investigated in both in vitro and in vivo experiments. Furthermore, RNA Sequencing, dual-luciferase reporter assays, and rescue tests were carried out to clarify its molecular process. We found that RP11-738E22.3 was substantially overexpressed in HCC tissues and linked to poor prognosis and unfavorable clinicopathological characteristics in HCC patients. Functionally, by upregulating FBXO6, an activator of the MAPK/ERK/mTOR signaling, RP11-738E22.3 stimulated HCC migration and proliferation in vitro and in vivo. Mechanically, RP11-738E22.3 regulated FBXO6 expression by competitively binding to miR-504-3p and miR-3135b, thereby activating the MAPK/ERK/mTOR pathway to suppress Autophagy and Apoptosis in HCC. In conclusion, lincRNA RP11-738E22.3 is a novel and promising biomarker for HCC progression, exerting its oncogenic effects through the inhibition of Autophagy and Apoptosis via activation of MAPK/ERK/mTOR signaling. Targeting RP11-738E22.3 may offer new therapeutic opportunities for HCC treatment.

Keywords
Apoptosis; Autophagy; Hepatocellular carcinoma; MAPK/ERK/mTOR pathway; RP11-738E22.3.
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