A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma

Abstract

The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptasefamily with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes. Effects of hTERTR-FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and tumors. Our results showed that the therapeutic effects of hTERTR-FAM96A were highly effective for inhibiting tumor growth and inducing apoptosis of hepatocellular carcinoma cells in H22-bearing nude mice. The hTERTR-FAM96A fusion protein could specifically bind with Apaf-1 and hTERT, which further induced apoptosis of hepatocellular carcinoma cells and improved apoptosis sensitivity. Our results indicated that hTERTR-FAM96A treatment enhanced cytotoxic effects by upregulation of cytotoxic T lymphocyte responses, interferon-γ release, and T lymphocyte infiltration. In addition, hTERTR-FAM96A led to tumor-specific immunologic cytotoxicity through increasing apoptotic body on hepatocellular tumors. Furthermore, hTERTR-FAM96A dramatically inhibited tumor growth, reduced death rate, and prolonged mice survival in hepatocellular carcinoma mice derived from three independent hepatocellular carcinoma mice cohorts compared to control groups. In summary, our data suggest that hTERTR-FAM96A may serve as an efficient anti-tumor agent for the treatment of hepatocellular carcinoma.

Telomerase reverse transcriptase suppression inhibits cell proliferation and promotes cell apoptosis in hepatocellular cancer

“…TERT , located at 5p15.33, which is a susceptibility region of lung cancer, was reported to be connected with pancreatic cancer risk . Human TERT ( hTERT ), an essential component of telomerase, was reported to be expressed in more than 80% of HCC cells . Some researchers suggested that hTERT expression and telomerase activity could serve as useful diagnostic markers in various malignancies .…”

Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

“…In collaboration with CIAO1, FAM96A matures ACO1 and stabilizes IREB2, thus connecting cytosolic iron-sulfur protein maturation with cellular iron regulation [29]. It has been shown that FAM96A increases cytotoxic T lymphocyte responses, interferon-γ release, and T lymphocyte infiltration [30]. Studies have shown that FAM96A is a novel pro-apoptotic tumor suppressor that is lost during tumorigenesis.…”

A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia

“…FAM96A and FAM96B participate in regulating tumor cell apoptosis by interacting with different proteins [ 47 ]. Some studies have shown that FAM96A can act as a tumor suppressor gene in various human cancers, including liver cancer [ 48 ]. But there is currently no detailed research report on the functional role of FAM96B in tumor progression at present.…”