No abstract

Long noncoding RNAs (lncRNAs) are a new class of regulatory noncoding RNAs. Emerging evidences indicate that lncRNAs play a critical role in the development of hepatocellular carcinoma (HCC). Although several lncRNAs have been annotated, the association of most lncRNAs with HCC is unknown. In this study, we investigated lncRNA alterations in HCC by performing lncRNA microarray analysis. We identified a novel lncRNA called HCC-associated lncRNA (HCAL) that was highly expressed in HCC tissues. HCAL upregulation was clinically associated with poor differentiation, intravascular cancer embolus, and decreased survival of patients with HCC. HCAL silencing significantly inhibited the growth and metastasis of HCC cells both in vitro and in vivo. Interestingly, transcriptome-sequencing analysis of HCAL-knockdown cells showed alterations in some cancer-related pathways. Mechanistically, HCAL directly interacted with and functioned as a sponge for microRNAs such as miR-15a, miR-196a, and miR-196b to modulate LAPTM4B expression. Taken together, our findings suggest the presence of a novel lncRNA-miRNA-mRNA regulatory network, i.e., the HCAL-miR-15a/miR-196a/miR-196b-LAPTM4B network, in HCC and indicate that HCAL may be a potential target for treating HCC.

Background: Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo. Results: In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice. Conclusion: Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be overexpressed in human cancers and act as a potential oncogene. However, little is known about the functional roles of UBE2C in HCC progression. In the present study, analysis of UBE2C mRNA expression in The Cancer Genome Atlas (TCGA) dataset reveals that significantly higher UBE2C mRNA levels was found in HCC tissues and associated with higher HCC grade. Elevated UBE2C mRNA levels in HCC indicated worsened survival probabilities. Through performing loss-of-function assays, we demonstrated that knockdown of UBE2C expression obviously suppressed proliferation, migration, and invasion of HCC cells in vitro. Moreover, HCC cells with UBE2C knockdown showed higher sensitivity for the treatment of chemotherapeutic drug, including adriamycin (ADR) and 5-fluorouracil (5-FU). Silencing of UBE2C also increased the sensitivity of HCC cells to sorafenib, an approved treatment for patients with advanced-stage HCC. Our findings strongly suggest that UBE2C emerges as a marker for prognosis in HCC, and blocking UBE2C may be a novel strategy for HCC therapies.

Recently, many studies show that long non-coding RNAs (lncRNAs) play important roles in cancer biology. Although its expression was reported dysregulated during tumorigenesis, the contributions of lncRNAs to hepatocellular carcinoma (HCC) are still largely unknown. In particular, the lncRNA CARLo-5 has a functional role in cell-cycle regulation in colon cancer, while the clinical significance and biological function of CARLo-5 in HCC remain unelucidated. In order to fill those study blanks, the expression level of CARLo-5 in human HCC specimens was tested, and its correlation with clinicopathologic features as well as the prognosis for patients with HCC was analyzed. Additionally, MTT, wound healing and transwell assays were employed to investigate the biological function of CARLo-5. The results showed that CARLo-5 levels were significantly overexpressed in HCC tissues compared to ANLT. Besides, high expression of CARLo-5 was associated with liver cirrhosis (P = 0.001), tumor number (P < 0.001), vascular invasion (P = 0.001), capsular formation (P = 0.014) and Edmondson-Steiner grade (P < 0.001), which proved that CARLo-5 was an independent risk factor for overall survival and disease-free survival. In addition, in highly metastatic HCC cell lines (HCCLM3 and MHCC97-L), CARLo-5 was up-regulated, but in lowly metastatic HCC cell lines (HepG2, SNU387), it showed down-regulated. Besides, by using gain and loss of function experiments in HCC cell lines (HCCLM3 and HepG2), the results showed that CARLo-5 overexpression significantly enhanced cell proliferation, migration and invasion in vitro. Our study also revealed that CARLo-5 was prominently up-regulated in HCC specimens and its high expression was associated with poor prognosis of HCC patients. Totally, those findings together indicate that CARLo-5 promotes proliferation and metastasis of HCC and potentially emerged as a novel therapeutic target.