Tongue cancer cells are known to be among the most aggressive cancers of the oral cavity. They spread rapidly, infiltrate lymphatic tissues, and often result in five-year survival rates of no more than 50 percent. For years, researchers have been asking the same question: is there a molecular vulnerability that can be targeted to stop them?
A recent study from the Faculty of Dentistry, Universitas Gadjah Mada, offers a promising answer. The study, published in the Journal of Taibah University Medical Sciences in November 2025, demonstrated that a synthetic molecule known as an antisense oligonucleotide (ASO) was able to significantly inhibit proliferation and induce apoptosis in human tongue squamous cell carcinoma cells.
The Prime Suspect: LINC00673
Behind the aggressiveness of tongue cancer, one name continues to appear in the molecular oncology literature: LINC00673. This is not an ordinary protein-coding gene. LINC00673 is a long non-coding RNA (lncRNA)—an RNA molecule longer than 200 nucleotides that does not produce proteins but can exert significant influence over cellular behavior.
Previous studies have reported that high LINC00673 expression in oral tongue squamous cell carcinoma is associated with larger tumor size, deeper local invasion, higher TNM stage, and lower overall survival. In short, the more LINC00673 present in tumor cells, the poorer the patient's prognosis.
This is where drg. Kadek Gede Putra Wibawa, MDSc, together with Prof. Supriatno, PhD, and Prof. Juni Handajani, PhD, from FKG UGM, began their approach. If LINC00673 is one of the drivers, then suppressing LINC00673 should, in theory, slow or stop cancer cell growth.
Molecular Strategy: Sending a Decoy to Destroy the Target
An antisense oligonucleotide is a synthetic single-stranded DNA or RNA sequence designed to recognize and bind specifically to a target RNA sequence, much like a key designed to fit a single lock. Once the ASO binds to LINC00673, the resulting RNA-ASO complex recruits the enzyme RNase H1, which then degrades the target RNA. As a result, the biological function of LINC00673 is disrupted.
In this study, H357 cells, a human tongue squamous cell carcinoma cell line, were used as the model. The research team synthesized an ASO with the specific sequence 5′-TGGCACCTCTTTCTTGTCCT-3′, designed using the sFold platform and subsequently validated using Nucleotide BLAST to confirm its specificity. The cells were then divided into several treatment groups: ASO, sense oligonucleotide (SO), scramble control oligonucleotide (SCO), transfection without oligonucleotides, and negative control.
Cell proliferation was measured using the MTT assay, while apoptosis was detected using acridine orange and ethidium bromide (AO-EB) double staining.
Cancer Cells Stop Growing—and Then Die
The results were striking. After 24 hours of incubation, all treatment groups showed reduced cell viability compared with the negative control. However, only the ASO group maintained a significant inhibitory effect on proliferation after 48 hours, across all tested concentrations, ranging from 1.56 to 12.5 μM. The SO and SCO groups showed no significant difference from the control on the second day.
The apoptosis findings were equally interesting. Under fluorescence microscopy, living cells appeared green, while apoptotic cells displayed yellow-green to orange-red fluorescence depending on the stage of cell death. The control, SO, and SCO groups were predominantly composed of green cells, indicating that the cells remained viable. In contrast, cells treated with LINC00673 ASO exhibited characteristic apoptotic morphological changes: chromatin condensation at a concentration of 6.25 μM and membrane blebbing at 12.5 μM.
“The percentage of apoptosis in cells treated with LINC00673 ASO reached 26% at a concentration of 6.25 μM and increased to 35.8% at 12.5 μM, with statistically significant differences compared with the control group.” — Wibawa et al., 2025
The consistent difference between the ASO and SCO groups provided evidence that the observed effects were on-target effects, rather than merely artifacts resulting from the transfection process.
From the Laboratory to Clinical Hope
This study does not represent a final victory over tongue cancer. The researchers themselves emphasized that it is an early-stage exploration. Direct measurement of LINC00673 expression levels, transfection efficiency, and the underlying biomolecular mechanisms still requires further investigation.
Nevertheless, the broader context cannot be ignored. In 2022, Indonesia was ranked among the countries with the highest incidence of oral cancer worldwide, with approximately 6,500 new cases. Tongue cancer accounts for more than 50 percent of all cases of oral squamous cell carcinoma, while survival rates have remained stagnant for decades.
ASO-based therapy is not a new concept in medicine, but its application to specific lncRNAs in tongue cancer remains relatively novel. In breast cancer, knockdown of LINC00673 using ASO has been shown to suppress cyclin D1 expression. In esophageal squamous cell carcinoma, inhibition of LINC00673 has been shown to trigger cell-cycle arrest. A similar pattern is now beginning to emerge in tongue cancer cells.
This research was funded by the Ministry of Higher Education, Science, and Technology (Kemendiktisaintek) through the PMDSU program, a scheme designed to support Indonesian master's students in completing research at a doctoral level. The fact that the findings were published in an international journal indexed by Elsevier is noteworthy in itself.
Tongue cancer has not been defeated. But a new vulnerability has now been identified, and researchers in Yogyakarta are taking a closer look at it.
Source DOI: https://doi.org/10.1016/j.jtumed.2025.10.007
Authors: Anny Anggraini; drg. Achmad Zam Zam Aghasy, M.Kes.
Photo: Freepik