# The Emerging Role of Long Noncoding RNAs in Sorafenib Resistance Within Hepatocellular Carcinoma
## 2 Long Noncoding RNAs (IncRNAs) in Sorafenib Resistance
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Long** & **Effects on** & & & \\
**Noncoding** & **Sorafenib** & **Target** & **Mechanisms Mediating Resistance/Major Effects** & **Reference** \\
**RNAs** & **Resistance** & & & \\ \hline  & & & & \\ \multirow{3}{*}{NEAT1} & \multirow{3}{*}{Promoting} & miR-149-5p & LncRNA NEAT1 modulates sorafenibb resistance in & \multirow{3}{*}{[122]} \\  & & miR-149-5p & hepatocellular carcinoma by regulating the & miR-149-5p/AKT1 axis & \\ \cline{3-5}  & & miR-335 & Mediating sorafenibb resistance by suppressing & \multirow{3}{*}{[123]} \\  & & miR-335 & miR-335 expression, and dis-inhibition on the & \\ \cline{3-5}  & & & c-Met-Akt signaling pathway & \\ \hline H19 & \multirow{3}{*}{Inhibiting} & miR-675 & Overexpression of H19 can reduce cell proliferation to reduce chemical resistance after sorafenibb & \multirow{3}{*}{[124]} \\  & & treatment & & \\ \hline  & & & & \\ \multirow{3}{*}{TUC338} & \multirow{3}{*}{Promoting} & \multirow{3}{*}{RASAL1} & TUC338, a lncRNA which is overexpressed in liver & \multirow{3}{*}{[125]} \\  & & cancer and may act as a tumor inducer, to illustrate & \\ \cline{3-5}  & & the function of lncRNA in the development process & & \\ \cline{3-5}  & & of chemoresistance in liver cancer in vitro and & \\ \cline{3-5}  & & in vivo. Functionally involved in sorafenibb resistance & \\ \cline{3-5}  & & hepatocarcinoma cells by targeting RASAL1 & \\ \hline ROR & Inhibiting & TGF-\(\beta\) & Sorafenibb increases expression of ROR in vesicles & \multirow{3}{*}{[126]} \\  & & inside and outside tumor cells, while siRNA to ROR & \\ \cline{3-5}  & & increases sensitivity to chemotherapy & \\ \hline HOTTIP & Inhibiting & HOXA13 & Stable overexpression of HOXA13 in liver cancer cell & \multirow{3}{*}{[127]} \\  & & lines increases cancer cell proliferation and migration & \\ \cline{3-5}  & & and reduces its sensitivity to sorafenibb & \\ \hline SNHG3 & Promoting & miR 128 & Inducing HCC cells EMT via miR 128/CD151 & \multirow{3}{*}{[87]} \\  & & cascade activation & & \\ \hline SNHG16 & Promoting & miR-140-5p & Functioning as an endogenous sponge for & \multirow{3}{*}{[122]} \\  & & miR-140-5p & miR-140-5p and the effects of SNHG16 knockdown on SR could be blocked by miR-140-5p inhibitor & \\ \hline FOXD2-AS1 & Inhibiting & miR-150-5p & Overexpression of FOXD2-AS1 overcame the & \multirow{3}{*}{[128]} \\  & & resistance of SR cells by functioningas a sponge for & \multirow{3}{*}{[129]} \\  & & miR-150-5p & miR-150-5p to modulate TMEM9 expression & \\ \hline SNHG1 & Promoting & miR-21 & LncRNA SNHG1 contributes to sorafenibb resistance & \multirow{3}{*}{[43]} \\  & & by activating the Akt pathway and is positively & \\ \cline{3-5}  & & regulated by miR-21 in hepatocellular carcinoma cells & \\ \hline HOTAIR & Promoting & miR-217 & LncRNA HOTAIR contributes to sorafenibb resistance & \multirow{3}{*}{[87]} \\  & & by suppressing miR-217 in hepatic carcinoma & \\ \hline TRERNA1 & Promoting & miR-22-3p & TRERNA1 upregulation mediated by Hbx promotes & \multirow{3}{*}{[130]} \\  & & sorafenib resistance and cell proliferation in HCC via & \\ \cline{3-5}  & & targeting N.R.A.S. by sponging miR-22-3p & \\ \hline TTN-AS1 & Promoting & miR-16-5p & LncRNA TTN-AS1 intensifies sorafenibb resistance in & \multirow{3}{*}{[129]} \\  & & hepatocellular carcinoma by sponging miR-16-5p & \\ \cline{3-5}  & & and upregulation of cyclin E1 & \\ \hline HEIH & Promoting & miR-98- & LncRNA H.E.I.H. confers cell sorafenibb resistance in & \multirow{3}{*}{[87]} \\  & & 5p/PI3K/AKT & hepatocellular carcinoma by regulating the & \\ \cline{3-5}  & & miR-98-5p/PI3K/AKT pathway & \\ \hline CRNDE & Inhibiting & miR-543 & LncRNA C.R.N.D.E. promotes ATG4B-mediated & \multirow{3}{*}{[130]} \\  & & autophagy and alleviates the sensitivity of sorafenibb & \\ \cline{3-5}  & & in hepatocellular carcinoma cells & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Studies identifying the lncRNA, including the target and mechanism of action.