Exosome‐transferred long non‐coding RNA ASMTL‐AS1 contributes to malignant phenotypes in residual hepatocellular carcinoma after insufficient radiofrequency ablation

Abstract

Objectives Long non‐coding RNAs (lncRNAs) are emerging RNA regulators in cancer progression, including in hepatocellular carcinoma (HCC). Recently, insufficient radiofrequency ablation (RFA) has been reported to lead to recurrence and metastasis of residual HCC tumours. Herein, we aimed to the role of ASMTL‐AS1 in residual HCC after insufficient RFA. Materials and methods In vitro insufficient RFA model was simulated in Huh7 cells and subsequently named Huh7‐H cells. In vitro and in vivo assays were conducted to investigate ASMTL‐AS1 function in HCC. Results LncRNA ASMTL‐AS1 low expressed in normal human liver was found to be highly expressed in HCC tissues and further increased in tumours after insufficient RFA. ASMTL‐AS1 expression was related to stage, metastasis and prognosis in HCC. Huh7‐H possessed higher ASMTL‐AS1 level and more aggressive than Huh7 cells. ASMTL‐AS1 contributed to the malignancy of HCC cells both in vitro and in vivo. Mechanistically, ASMTL‐AS1 was trans‐activated by MYC and promoted NLK expression to activate YAP signalling via sequestering miR‐342‐3p in HCC. Interestingly, ASMTL‐AS1 could be wrapped by exosomes and then convey malignancy through NLK/YAP axis between cells even in residual HCC after insufficient RFA. Conclusions Exosomal ASMTL‐AS1 aggravates the malignancy in residual HCC after insufficient RFA via miR‐342‐3p/NLK/YAP signalling, opening a new road for the treatment of HCC and the prevention of recurrence or metastasis of residual HCC after insufficient RFA.

A Novel Tumor Suppressor ASMTL-AS1 Regulates the Mir-1228-3p/SOX17/Β-Catenin Axis in Triple-Negative Breast Cancer

“…Feng et al reported that ASMTL-AS1 was signi cantly downregulated in papillary thyroid carcinoma, which served as a tumor suppressor via inhibiting cell growth and glycolysis [13]. However, another study showed that ASMTL-AS1 was an oncogene in hepatocellular carcinoma that activated carcinogenic YAP signaling and promoted cancer recurrence or metastasis [14]. Herein, we found that ASMTL-AS1 was a tumor-inhibiting lncRNA in TNBC, inactivating oncogenic Wnt/β-catenin pathway and repressing cell proliferation and invasion, and restoration of ASMTL-AS1 expression signi cantly retarded the growth of tumor in vivo.…”

“…Extensive studies have shown that lncRNA serves as a ceRNA in various human diseases, such as the lnc-BCYRN1/miR-619-5p/CUEDC2 axis in glioma [10], lnc-DNM3OS/miR-126/IGF1 axis in osteoarthritis [11], and lnc-UCA1/miR-182-5p/DLL4 axis in renal cancer [12]. ASMTL-AS1 is a newly found lncRNA that locates at Xp22.33 and Yp11.2, which has been recently reported as a key player in papillary thyroid cancer [13] and hepatocellular carcinoma [14], and could be used as a prognostic biomarker for bladder cancer [15]. Nevertheless, its role in TNBC remains unknown.…”

Exosome in Hepatocellular Carcinoma: an update

“…Subsequently, the research results on exosomal lncRNAs gradually increased. Using Huh7 cells in vitro to simulate the insufficient radiofrequency ablation (RFA), the researcher found that exosomal lncRNA ASMTL-AS1 activated miR-342-3p/NLK/YAP signals, aggravating residual malignant hepatocellular carcinoma when RFA was insufficient, opening up a new way for the treatment of HCC and preventing its recurrence 42 . Wang et al measured the expression of lncRNA H19 in HCC by qRT-PCR and western blot, and found that it could up-regulate LIMK1 and inhibit apoptosis, promote the proliferation, migration, and metastasis of HCC treated with propanol 43 .…”

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

“…For example, lncRNA H19 promotes proliferation and migration but inhibits apoptosis of HCC cells via sponging miR-520a-3p, thereby, upregulating the LIMK1 gene that encodes the LIM domain kinase 1 protein (111). Additionally, exosomal lncRNA ASMTL-AS1 can promote HCC malignancy via sponging miR-342-3p and transactivating c-Myc to promote oncogenic MAPK family Nemo-like kinase (NLK) expression and yes-associated protein 1 (YAP) activation (112).…”