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Long Noncoding RNAs Coregulated by Annexin A7 and JNK in Hepatocellular Carcinoma Cells Identified by Whole-Genome
Qi Deng1, Lianhong Li2, Yanling Jin1
1Department of Pathology, First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Dalian, Liaoning, China.
Abstract:
Knockdown of Annexin A7 (ANXA7) or C-Jun N-terminal kinase (JNK) inhibits the proliferation, migration, invasion, and lymphatic adhesion of hepatocellular carcinoma (HCC) cells, suggesting that ANXA7 and JNK signaling pathways contribute to HCC growth and lymph node metastasis (LNM). While the intervening molecular pathways are largely unknown, emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in ANXA7 and JNK signaling. To identify potential therapeutic targets for HCC, we screened for lncRNAs differentially expressed among Hca-P cells stably expressing shRNA-ANXA7, shRNA-JNK, or control-shRNA. RNA sequencing identified 216 lncRNAs differentially expressed between shRNA-ANXA7 and control-shRNA cells, of which 101 were downregulated and 115 upregulated, as well as 436 lncRNAs differentially expressed between shRNA-JNK and control-shRNA cells, of which 236 were downregulated and 200 upregulated. Fifty-six lncRNAs were differentially expressed under both ANXA7 and JNK knockdown. We selected 4 of these for verification based on putative involvement in cancer regulation according to GO and KEEG analyses of target genes. Knockdown of ANXA7 or JNK suppressed expression of NONMMUT012084.2, NONMMUT024756.2, and ENSMUST00000130486, and enhanced expression of ENSMUST00000197932. These lncRNAs are intriguing candidate targets for mechanistic analysis of HCC progression and therapeutic intervention.
Insights
Knockdown of Annexin A7 (ANXA7) and C-Jun N-terminal kinase (JNK) inhibits hepatocellular carcinoma (HCC) progression. This study identifies specific long noncoding RNAs (lncRNAs) affected by ANXA7 and JNK, offering potential therapeutic targets for HCC and lymph node metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Annexin A7 (ANXA7) and C-Jun N-terminal kinase (JNK) signaling pathways are implicated in hepatocellular carcinoma (HCC) growth and lymph node metastasis (LNM).
- The molecular mechanisms linking ANXA7, JNK, and HCC progression, particularly the role of long noncoding RNAs (lncRNAs), remain largely unexplored.
Purpose of the Study:
- To identify novel long noncoding RNAs (lncRNAs) involved in Annexin A7 (ANXA7) and C-Jun N-terminal kinase (JNK) signaling pathways in hepatocellular carcinoma (HCC).
- To explore potential therapeutic targets for inhibiting HCC proliferation, migration, invasion, and lymph node metastasis.
Main Methods:
- RNA sequencing was performed on hepatocellular carcinoma (HCC) cells with stable knockdown of Annexin A7 (ANXA7) or C-Jun N-terminal kinase (JNK).
- Differential expression analysis identified lncRNAs affected by ANXA7 and JNK knockdown.
- Gene Ontology (GO) and KEGG pathway analyses were used to assess the putative roles of selected lncRNAs in cancer regulation.
Main Results:
- Knockdown of ANXA7 or JNK significantly altered the expression of numerous lncRNAs in HCC cells.
- Fifty-six lncRNAs were found to be differentially expressed under both ANXA7 and JNK knockdown conditions.
- Specific lncRNAs, including NONMMUT012084.2, NONMMUT024756.2, and ENSMUST00000130486, were suppressed, while ENSMUST00000197932 was enhanced by ANXA7 or JNK knockdown.
Conclusions:
- The identified lncRNAs are significantly regulated by ANXA7 and JNK signaling in HCC.
- These lncRNAs represent promising candidate targets for further mechanistic studies and potential therapeutic interventions in hepatocellular carcinoma (HCC) and its associated lymph node metastasis (LNM).
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